33 results on '"Association RETINA France"'
Search Results
2. Altered visual processing in the mdx52 mouse model of Duchenne muscular dystrophy
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Alvaro Rendon, Anneka Joachimsthaler, Cyrille Vaillend, Jerome E. Roger, Jan Kremers, Dora Fix Ventura, Mirella Telles Salgueiro Barboni, Andre Liber, Amel Saoudi, Aurélie Goyenvalle, Semmelweis University [Budapest], University of São Paulo (USP), Section for Retinal Physiology, University Hospital Erlangen, Friedrich-Alexander Universität Erlangen-Nürnberg (FAU), Handicap neuromusculaire : Physiopathologie, Biothérapie et Pharmacologies appliquées (END-ICAP), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Sction for Retinal Physiology, University Hospital Erlangen, This study was supported by the Centre National de la Recherche Scientifique (CNRS), the Universit ́e Paris-Sud (France), the DIM Gene Therapy Region Ile-de-France to JER, the Deutscher Akademischer Austauschdienst (DAAD #57513929) in Germany and Tempus Public Foundation in Hungary to JK and MTSB, the Sao Paulo Research Foundation (FAPESP # 2019/007771 to AMPL, 2016/04538–3 and 2014/26818–2 to DFV), the National Council for Scientific and Tech-nological Development (CNPq grant number 404239/2016–1 to MTSB), a project award from the Association Mon ́egasque contre les Myopathies (AMM, Monaco) to CV, a National Research, Development, and Inno-vation Fund of Hungary OTKA (PD134799), a fellowship from Campus France (dossier 931,824 L) and a short-term scientific mission from COST Action CA17103 to MTSB and a CNPq 1A productivity fellowship (CNPq 309,409/2015–2) to DFV., PERIGNON, Alain, Universidade de São Paulo = University of São Paulo (USP), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Duchenne muscular dystrophy ,Photoreceptors ,genetic structures ,Mesopic vision ,Dp427 ,media_common.quotation_subject ,B-wave ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV.NEU.PC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,Biology ,Synaptic Transmission ,Retina ,lcsh:RC321-571 ,Mouse model ,Dystrophin ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,medicine ,Electroretinography ,Contrast (vision) ,Animals ,Scotopic vision ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,media_common ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Retinal ,Electroretinogram ,medicine.disease ,Muscular Dystrophy, Duchenne ,030104 developmental biology ,Neurology ,chemistry ,Optomotor response ,Mice, Inbred mdx ,Visual Perception ,Dp260 ,Dp140 ,sense organs ,Erg ,Neuroscience ,[SDV.NEU.SC] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,030217 neurology & neurosurgery ,Photopic vision - Abstract
International audience; The mdx52 mouse model of Duchenne muscular dystrophy (DMD) is lacking exon 52 of the DMD gene that is located in a hotspot mutation region causing cognitive deficits and retinal anomalies in DMD patients. This deletion leads to the loss of the dystrophin proteins, Dp427, Dp260 and Dp140, while Dp71 is preserved. The flash electroretinogram (ERG) in mdx52 mice was previously characterized by delayed dark-adapted b-waves. A detailed description of functional ERG changes and visual performances in mdx52 mice is, however, lacking. Here an extensive full-field ERG repertoire was applied in mdx52 mice and WT littermates to analyze retinal physiology in scotopic, mesopic and photopic conditions in response to flash, sawtooth and/or sinusoidal stimuli. Behavioral contrast sensitivity was assessed using quantitative optomotor response (OMR) to sinusoidally modulated luminance gratings at 100% or 50% contrast. The mdx52 mice exhibited reduced amplitudes and delayed implicit times in dark-adapted ERG flash responses, particularly in their b-wave and oscillatory potentials, and diminished amplitudes of light-adapted flash ERGs. ERG responses to sawtooth stimuli were also diminished and delayed for both mesopic and photopic conditions in mdx52 mice and the first harmonic amplitudes to photopic sine-wave stimuli were smaller at all temporal frequencies. OMR indices were comparable between genotypes at 100% contrast but significantly reduced in mdx52 mice at 50% contrast. The complex ERG alterations and disturbed contrast vision in mdx52 mice include features observed in DMD patients and suggest altered photoreceptor-to-bipolar cell transmission possibly affecting contrast sensitivity. The mdx52 mouse is a relevant model to appraise the roles of retinal dystrophins and for preclinical studies related to DMD.
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- 2021
3. YAP protects the eye from uveitic glaucoma by preserving retinal and anterior chamber homeostases
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Bitard, Juliette, Grellier, Elodie-Kim, Lourdel, Sophie, Filipe, Helena, Hamon, Annaïg, Fenaille, François, Castelli, Florence, Chu-Van, Emeline, Roger, Jérôme E., Locker, Morgane, Perron, Muriel, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Universidade de Lisboa = University of Lisbon (ULISBOA), Institut de recherche en santé, environnement et travail (Irset), Université d'Angers (UA)-Université de Rennes (UR)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), CEA- Saclay (CEA), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Retina France, UNADEV, ARVO Association for Research in Vision and Ophthalmology, Universidade de Lisboa (ULISBOA), Université d'Angers (UA)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Université Paris-Saclay
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genetic structures ,[SDV]Life Sciences [q-bio] ,sense organs ,ComputingMilieux_MISCELLANEOUS ,eye diseases - Abstract
https://iovs.arvojournals.org/article.aspx?articleid=2775349; International audience; The role of the transcription coactivator YAP has been studied during eye development but its implication in ocular homeostasis and diseases is much less documented. YAP is expressed by several ocular cell types including the non-pigmented cells of the ciliary body (CB) as well as Müller glial cells (MGs) of the neuroretina. Here, we assessed whether postnatal Yap deletion in these two cell types could affect eye homeostasis during aging.Methods : Specific Yap deletion in CB and MGs was induced in a conditional mouse model (Yap cKO) at P10. The phenotype was investigated by western-blot, immunohistochemistry, and RNA-sequencing (RNA-seq). Blood defects were identified by fluorescein angiography. Optic nerve degeneration was assessed by optical coherence tomography. Intraocular pressure (IOP) was recorded by a rebound tonometer. Imaging of the CB in healthy and uveitic human patients was performed by ultrasound biomicroscopy.
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- 2021
4. Modeling ocular lens disease in Xenopus
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Justine Viet, Carole Gautier-Courteille, Serge Hardy, David Reboutier, Luc Paillard, Salil A. Lachke, Institut de Génétique et Développement de Rennes (IGDR), Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), University of Delaware [Newark], Association Retina France, Bouygues, Centre National de la Recherche Scientifique-PICS, R01EY021505, NIH Blueprint for Neuroscience Research, R01EY029770, NIH Blueprint for Neuroscience Research, and Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )
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0301 basic medicine ,Visual acuity ,genetic structures ,[SDV]Life Sciences [q-bio] ,ved/biology.organism_classification_rank.species ,Xenopus ,Biology ,Article ,03 medical and health sciences ,Xenopus laevis ,0302 clinical medicine ,Cataracts ,Lens, Crystalline ,medicine ,Animals ,Humans ,Clustered Regularly Interspaced Short Palindromic Repeats ,Model organism ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,ved/biology ,medicine.disease ,biology.organism_classification ,Lens Fiber ,eye diseases ,3. Good health ,Cell biology ,PAX6 ,GJA8 ,030104 developmental biology ,medicine.anatomical_structure ,cataract ,Lens (anatomy) ,CRISPR ,Eye development ,pathology ,sense organs ,medicine.symptom ,030217 neurology & neurosurgery ,DNASE2B ,Developmental Biology - Abstract
International audience; BACKGROUND:Ocular lens clouding is termed as cataract, which depending on the onset, is classified as congenital or age-related. Developing new cataract treatments requires new models. Thus far, Xenopus embryos have not been evaluated as a system for studying cataract.RESULTS:We characterized the developmental process of lens formation in Xenopus laevis tailbuds and tadpoles, and we disrupted the orthologues of three mammalian cataract-linked genes in F0 by CRISPR/Cas9. We assessed the consequences of gene inactivation by combining external examination with histochemical analyses and functional vision assays. Inactivating the key metazoan eye development transcription factor gene pax6 produces a strong eye phenotype including an absence of eye tissue. Inactivating the genes for gap-junction protein and a nuclease, gja8 and dnase2b, produces lens defects that share several features of human cataracts, including impaired vision acuity, nuclei retention in lens fiber cells, and actin fibers disorganization. We tested the potential improvement of the visual acuity of gja8 crispant tadpoles upon treatment with the molecular chaperone 4-phenylbutyrate.CONCLUSION:Xenopus is a valuable model organism to understand the molecular pathology of congenital eye defects, including cataracts, and to screen molecules with a potential to prevent or reverse cataracts.
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- 2020
5. Pias3 is necessary for dorso-ventral patterning and visual response of retinal cones but is not required for rod photoreceptor differentiation
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Hannah Breit, Anand Swaroop, Jerome E. Roger, Christie K Campla, Jessica D. Gumerson, Lijin Dong, National Institutes of Health [Bethesda] (NIH), National Eye Institute [Bethesda, MD, États-Unis] (NEI), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Institut des Neurosciences Paris-Saclay (NeuroPSI), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,genetic structures ,Vision ,QH301-705.5 ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Science ,Stimulation ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Retina development ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Mouse knockout ,Protein inhibitor of activated STAT ,Biology (General) ,Genetics ,Regulation of gene expression ,Retina ,medicine.diagnostic_test ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Retinal ,eye diseases ,SUMOylation ,Cell biology ,Gene regulation ,030104 developmental biology ,medicine.anatomical_structure ,chemistry ,Cell type specification ,sense organs ,General Agricultural and Biological Sciences ,030217 neurology & neurosurgery ,Electroretinography ,Visual phototransduction ,Photopic vision ,Research Article - Abstract
Protein inhibitor of activated Stat 3 (Pias3) is implicated in guiding specification of rod and cone photoreceptors through post-translational modification of key retinal transcription factors. To investigate its role during retinal development, we deleted exon 2-5 of the mouse Pias3 gene, which resulted in complete loss of the Pias3 protein. Pias3−/− mice did not show any overt phenotype, and retinal lamination appeared normal even at 18 months. We detected reduced photopic b-wave amplitude by electroretinography following green light stimulation of postnatal day (P)21 Pias3−/− retina, suggesting a compromised visual response of medium wavelength (M) cones. No change was evident in response of short wavelength (S) cones or rod photoreceptors until 7 months. Increased S-opsin expression in the M-cone dominant dorsal retina suggested altered distribution of cone photoreceptors. Transcriptome profiling of P21 and 18-month-old Pias3−/− retina revealed aberrant expression of a subset of photoreceptor genes. Our studies demonstrate functional redundancy in SUMOylation-associated transcriptional control mechanisms and identify a specific, though limited, role of Pias3 in modulating spatial patterning and optimal function of cone photoreceptor subtypes in the mouse retina., Summary: Loss of Pias3 in mice results in altered dorso-ventral patterning of retinal cone photoreceptors by modulating the expression of a subset of genes, but does not affect rod development.
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- 2017
6. Usher syndrome type 1–associated cadherins shape the photoreceptor outer segment
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Amrit Estivalet, Asadollah Aghaie, Aziz El-Amraoui, Cataldo Schietroma, Karine Parain, José-Alain Sahel, Muriel Perron, Christine Petit, Jacques Boutet de Monvel, Serge Picaud, Syndrome de Usher et autres atteintes rétino-cochléaires, Institut de la Vision, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Génétique et Physiologie de l'Audition, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ED 515 - Complexité du vivant, Université Pierre et Marie Curie - Paris 6 (UPMC), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Collège de France (CdF (institution)), This work was supported by the FAUN Stiftung (Suchert Foundation), LHW-Stiftung, Retina France, the European Research Council advanced grant 'Hair bundle' (ERC-2011-AdG 294570), the European Union Seventh Framework Program, under grant agreement HEALTH-F2-2010-242013 (TREATRUSH), the French Agence Nationale pour la Recherche as part of the second Investissements d’Avenir program (light4deaf, ANR-15-RHUS-0001), and the LabEx Lifesenses (ANR-10-LABX-65)., ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), European Project: 294570,EC:FP7:ERC,ERC-2011-ADG_20110310,HAIRBUNDLE(2012), European Project: 242013,EC:FP7:HEALTH,FP7-HEALTH-2009-single-stage,TREATRUSH(2010), Oficjalska, Danuta, Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, Assembling the puzzle of the operating auditory hair bundle - HAIRBUNDLE - - EC:FP7:ERC2012-12-01 - 2017-11-30 - 294570 - VALID, Fighting blindness of Usher syndrome: diagnosis, pathogenesis and retinal treatment (TreatRetUsher) - TREATRUSH - - EC:FP7:HEALTH2010-02-01 - 2014-01-31 - 242013 - VALID, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Chaire Génétique et physiologie cellulaire
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0301 basic medicine ,genetic structures ,Xenopus ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Xenopus Proteins ,Article ,03 medical and health sciences ,0302 clinical medicine ,CDH23 ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,otorhinolaryngologic diseases ,medicine ,Animals ,Research Articles ,Actin ,Retina ,Gene knockdown ,biology ,Cadherin ,Usher Syndrome Type 1 ,Gene Expression Regulation, Developmental ,Cell Biology ,Anatomy ,Cadherins ,Retinal Photoreceptor Cell Outer Segment ,Rod Cell Outer Segment ,biology.organism_classification ,Photoreceptor outer segment ,eye diseases ,Cell biology ,Actin Cytoskeleton ,030104 developmental biology ,medicine.anatomical_structure ,Gene Knockdown Techniques ,Larva ,Retinal Cone Photoreceptor Cells ,sense organs ,Usher Syndromes ,030217 neurology & neurosurgery - Abstract
Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but USH1 protein function in the retina is unclear. Schietroma et al. use Xenopus to model the deficiency in two USH1 proteins—protocadherin-15 and cadherin-23—and identify crucial roles for these molecules in shaping the photoreceptor outer segment., Usher syndrome type 1 (USH1) causes combined hearing and sight defects, but how mutations in USH1 genes lead to retinal dystrophy in patients remains elusive. The USH1 protein complex is associated with calyceal processes, which are microvilli of unknown function surrounding the base of the photoreceptor outer segment. We show that in Xenopus tropicalis, these processes are connected to the outer-segment membrane by links composed of protocadherin-15 (USH1F protein). Protocadherin-15 deficiency, obtained by a knockdown approach, leads to impaired photoreceptor function and abnormally shaped photoreceptor outer segments. Rod basal outer disks displayed excessive outgrowth, and cone outer segments were curved, with lamellae of heterogeneous sizes, defects also observed upon knockdown of Cdh23, encoding cadherin-23 (USH1D protein). The calyceal processes were virtually absent in cones and displayed markedly reduced F-actin content in rods, suggesting that protocadherin-15–containing links are essential for their development and/or maintenance. We propose that calyceal processes, together with their associated links, control the sizing of rod disks and cone lamellae throughout their daily renewal.
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- 2017
7. Retinal Degeneration Triggers the Activation of YAP/TEAD in Reactive Müller Cells
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Hamon, Annaïg, Masson, Christel, Bitard, Juliette, Gieser, Linn, Roger, Jérôme E., Perron, Muriel, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), National Institutes of Health [Bethesda] (NIH), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, and Partenaires INRAE-Partenaires INRAE
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MESH: Signal Transduction ,retina ,MESH: Retinal Degeneration ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Blotting, Western ,Ependymoglial Cells ,Hippo/YAP pathway ,Cell Cycle Proteins ,Real-Time Polymerase Chain Reaction ,MESH: Phosphoproteins ,Mice ,MESH: Photoreceptor Cells ,MESH: Mice, Inbred C57BL ,MESH: Blotting, Western ,Animals ,MESH: Animals ,Photoreceptor Cells ,RNA, Messenger ,MESH: Mice ,MESH: Adaptor Proteins, Signal Transducing ,MESH: RNA, Messenger ,photoreceptor degeneration ,Adaptor Proteins, Signal Transducing ,Müller cells ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,MESH: Real-Time Polymerase Chain Reaction ,Retinal Degeneration ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Nuclear Proteins ,TEA Domain Transcription Factors ,MESH: Immunohistochemistry ,YAP-Signaling Proteins ,MESH: Transcription Factors ,MESH: Ependymoglial Cells ,Phosphoproteins ,MESH: Gene Expression Regulation ,Immunohistochemistry ,DNA-Binding Proteins ,Mice, Inbred C57BL ,Disease Models, Animal ,Retinal Cell Biology ,Gene Expression Regulation ,sense organs ,MESH: Disease Models, Animal ,MESH: Nuclear Proteins ,MESH: DNA-Binding Proteins ,Signal Transduction ,Transcription Factors - Abstract
Purpose During retinal degeneration, Müller glia cells respond to photoreceptor loss by undergoing reactive gliosis, with both detrimental and beneficial effects. Increasing our knowledge of the complex molecular response of Müller cells to retinal degeneration is thus essential for the development of new therapeutic strategies. The purpose of this work was to identify new factors involved in Müller cell response to photoreceptor cell death. Methods Whole transcriptome sequencing was performed from wild-type and degenerating rd10 mouse retinas at P30. The changes in mRNA abundance for several differentially expressed genes were assessed by quantitative RT-PCR (RT-qPCR). Protein expression level and retinal cellular localization were determined by western blot and immunohistochemistry, respectively. Results Pathway-level analysis from whole transcriptomic data revealed the Hippo/YAP pathway as one of the main signaling pathways altered in response to photoreceptor degeneration in rd10 retinas. We found that downstream effectors of this pathway, YAP and TEAD1, are specifically expressed in Müller cells and that their expression, at both the mRNA and protein levels, is increased in rd10 reactive Müller glia after the onset of photoreceptor degeneration. The expression of Ctgf and Cyr61, two target genes of the transcriptional YAP/TEAD complex, is also upregulated following photoreceptor loss. Conclusions This work reveals for the first time that YAP and TEAD1, key downstream effectors of the Hippo pathway, are specifically expressed in Müller cells. We also uncovered a deregulation of the expression and activity of Hippo/YAP pathway components in reactive Müller cells under pathologic conditions.
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- 2017
8. Five simultaneous artificial intelligence data challenges on ultrasound, CT, and MRI
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B. Bresson, N. Poussange, M. Majer, Marc Zins, D. Guenoun, Olivier Hauger, S. Si-Mohamed, D. Istrati, Théo Estienne, M. Azoulay, S. Molière, Nathalie Lassau, E. Jehanno, C. Balleyguier, Caroline Caramella, A. Bergère, M. Boisserie, J. Behr, F. Dubrulle, J.-F. Meder, François Cornelis, E. Poncelet, A. Paisant, Raphaëlle Renard-Penna, N. Peyron Faure, H. Cauliez, Caroline Malhaire, T. Caramella, A. Perrey, P. de Vomecourt, François Bidault, C. Bordonne, S. Montagne, Alain Luciani, S. Caius Giurca, G. Garcia, M. Faivre-Pierre, Nicolas Amoretti, F. Desmots, Anne Cotten, M. Abitbol, V. Herreros, Aurélie Jalaguier-Coudray, Olivier Rouvière, J.-F. Budzik, J. Cagnol, Laure Fournier, Valérie Juhan, M. Faruch, C. Cyteval, T. Jacques, J. Bocquet, R. Lotte, T. Willaume, J.-L. Drape, S. Brunelle, A. Blum, M. Garetier, L. Di Marco, F. Pigneur, Institut Gustave Roussy (IGR), Imagerie multimodale en cancérologie. (IR4M/U8081 éq.3), Institut Gustave Roussy (IGR)-Imagerie par Résonance Magnétique Médicale et Multi-Modalités (IR4M), Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Bicêtre-Centre National de la Recherche Scientifique (CNRS), Direction de la recherche [Gustave Roussy], Radiothérapie Moléculaire et Innovation Thérapeutique (RaMo-IT), Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Direction de la Transformation Numérique et des Systèmes d’Information, Mathématiques et Informatique pour la Complexité et les Systèmes (MICS), CentraleSupélec-Université Paris-Saclay, Comité de Cancérologie (CCAFU), Association Française d'Urologie, Département de radiothérapie [Gustave Roussy], Service de Radiologie et Imagerie Musculosquelettique, Centre de Consultations et d’Imagerie de l’Appareil Locomoteur, Service de Radiologie (LILLE - Radio), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de radiologie [CHRU Besancon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Clinique du sport de Bordeaux-Mérignac, Clinique Saint-Jean - Toulon, Polytech'Paris - Sorbonne Université, Sorbonne Université (SU), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Centre Hospitalier Universitaire de Nice (CHU Nice), inconnu temporaire UPEMLV, Inconnu, Service de radiologie et imagerie médicale [Rennes] = Radiology [Rennes], CHU Pontchaillou [Rennes], Application des ultrasons à la thérapie (LabTAU), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Centre de résonance magnétique des systèmes biologiques (CRMSB), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), Hôpital d'Instruction des Armées Clermont Tonnerre, Service de Santé des Armées, Hôpital Henri Mondor, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Department of Radiology, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université de Lyon, Hôpital Cochin [AP-HP], Service Imagerie de la femme, CH de Valenciennes, Hôpital Hôtel-Dieu [Paris], Centre Hospitalier de Lens, Université catholique de Lille (UCL), Institut Bergonié [Bordeaux], UNICANCER, Hôpital de Hautepierre [Strasbourg], Clinique du Val d'Ouest, Centre d’ Imagerie du Chinonais, Hôpital Européen [Fondation Ambroise Paré - Marseille], Institut du Sein, Service de Génétique Médicale [CHU Clermont-Ferrand], CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand-CHU Clermont-Ferrand, Service de Pathologie Infectieuse et Tropicale [HIA Laveran, Marseille], Hôpital d'instruction des armées Laveran, Clinique du Pont Saint-Vaast, Douai, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Département de Radiologie, Armentières (59), Hôpital Sainte-Marguerite [CHU - APHM] (Hôpitaux Sud ), Institut des Sciences du Mouvement Etienne Jules Marey (ISM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Sciences pour l'environnement (SPE), Université Pascal Paoli (UPP)-Centre National de la Recherche Scientifique (CNRS), Centre hospitalier Saint-Joseph [Paris], Service de neuroradiologie [Paris], Hôpital Sainte-Anne, Marrow Adiposity & Bone Lab - Adiposité Médullaire et Os - ULR 4490 (MABLab (ex-pmoi)), Université du Littoral Côte d'Opale (ULCO)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Radiologie Viscèrale, CHRU de Jean-Minjoz, CHU Toulouse [Toulouse], Service de radiologie et imagerie médicale [Rennes], Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-CHU Pontchaillou [Rennes], Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM), Résonance magnétique des systèmes biologiques (RMSB), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), CHU Clermont-Ferrand, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre National de la Recherche Scientifique (CNRS)-Aix Marseille Université (AMU), Centre National de la Recherche Scientifique (CNRS)-Université Pascal Paoli (UPP), Groupe hospitalier Paris Saint-Joseph - Hôpital, Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CCSD, Accord Elsevier, Imagerie par Résonance Magnétique Médicale et Multi-Modalités (IR4M), Centre National de la Recherche Scientifique (CNRS)-Hôpital Bicêtre-Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)-Hôpital Bicêtre-Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR), and Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB)
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Kidney Cortex ,[SPI] Engineering Sciences [physics] ,Interprofessional Relations ,education ,Meniscal tears ,Datasets as Topic ,Computed tomography ,Breast Neoplasms ,Artificial intelligence (AI) ,030218 nuclear medicine & medical imaging ,03 medical and health sciences ,[SPI]Engineering Sciences [physics] ,0302 clinical medicine ,Multidisciplinary approach ,Artificial Intelligence ,Ultrasound ,Medicine ,Data Protection Act 1998 ,Humans ,Radiology, Nuclear Medicine and imaging ,Neoplasm Invasiveness ,Thyroid Neoplasms ,Magnetic resonance imaging (MRI) ,Computer Security ,Ultrasonography ,Modalities ,Radiological and Ultrasound Technology ,medicine.diagnostic_test ,business.industry ,Communication ,Liver Neoplasms ,Computed Tomography (CT) ,Deep learning ,General Medicine ,Magnetic Resonance Imaging ,Tibial Meniscus Injuries ,030220 oncology & carcinogenesis ,General Data Protection Regulation ,Thyroid Cartilage ,Artificial intelligence ,business ,Tomography, X-Ray Computed - Abstract
Summary Purpose The goal of this data challenge was to create a structured dynamic with the following objectives: (1) teach radiologists the new rules of General Data Protection Regulation (GDPR), while building a large multicentric prospective database of ultrasound, computed tomography (CT) and MRI patient images; (2) build a network including radiologists, researchers, start-ups, large companies, and students from engineering schools, and; (3) provide all French stakeholders working together during 5 data challenges with a secured framework, offering a realistic picture of the benefits and concerns in October 2018. Materials and methods Relevant clinical questions were chosen by the Societe Francaise de Radiologie. The challenge was designed to respect all French ethical and data protection constraints. Multidisciplinary teams with at least one radiologist, one engineering student, and a company and/or research lab were gathered using different networks, and clinical databases were created accordingly. Results Five challenges were launched: detection of meniscal tears on MRI, segmentation of renal cortex on CT, detection and characterization of liver lesions on ultrasound, detection of breast lesions on MRI, and characterization of thyroid cartilage lesions on CT. A total of 5,170 images within 4 months were provided for the challenge by 46 radiology services. Twenty-six multidisciplinary teams with 181 contestants worked for one month on the challenges. Three challenges, meniscal tears, renal cortex, and liver lesions, resulted in an accuracy > 90%. The fourth challenge (breast) reached 82% and the lastone (thyroid) 70%. Conclusion Theses five challenges were able to gather a large community of radiologists, engineers, researchers, and companies in a very short period of time. The accurate results of three of the five modalities suggest that artificial intelligence is a promising tool in these radiology modalities.
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- 2019
9. Real-world outcomes of observation and treatment in diabetic macular edema with very good visual acuity: the OBTAIN study
- Author
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Jay Chhablani, Jan Darius Unterlauft, Zafer Cebeci, Dinah Zur, Matias Iglicki, Inês Laíns, Mali Okada, Anna Sala-Puigdollers, Catharina Busch, Anat Loewenstein, Voraporn Chaikitmongkol, Ana Rita Santos, Marco Lupidi, Paradee Kunavisarut, Patricio J. Rodríguez-Valdés, Matus Rehak, Samantha Fraser-Bell, Adrian T. Fung, Pierre-Henry Gabrielle, Assaf Hilely, Małgorzata Ozimek, Ermete Giancipoli, Laboratoire LTEE, University of Sydney, Tel-Aviv Sourasky Medical Center, Tecnológico de Monterrey (ITESM), Istanbul University, Università degli Studi di Perugia (UNIPG), Westmead Hospital [Sydney], Macquarie University, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Université Bourgogne Franche-Comté [COMUE] (UBFC), Università degli Studi di Sassari, Chiang Mai University (CMU), Royal Melbourne Hospital, Universidade de Coimbra, Association for Innovation and Biomedical Research on Light and Image (AIBILI), Harvard Medical School [Boston] (HMS), Polytechnic Institute of Porto, Hospital Clínic de Barcelona, L.V. Prasad Eye Institute, Partenaires INRAE, Medical University in Lublin, National University of Central Buenos Aires, Retina Australia, Retina Pigmentosa ASBL, Retina Brazil, The Foundation Fighting Blindness, Retina Ry / Retina Finland, Association RETINA France, PRO RETINA Deutschland e. V., Hellenic Retina Society, Hong Kong, For Our Sight Foundation, Blindrafélagið, Icelandic Association of the visually impaired (BIAVI) (Retina Iceland), Blindrafelagid – Retina Iceland, Fighting Blindness, Certo Clav, Retina Itialia, Japanese Retinitis Pigmentosa Society, Patientengroep Retina, Retina New Zealand Inc., Retinitis Pigmentosa Foreningen i Norge, Pakistan Foundation Fighting Blindness, ARP (Portuguese Association of RP), Retina South Africa, Svenska RP-Föreningen, RETINITIS PIGMENTOSA TAIPEI, RP Fighting Blindness, Foundation Fighting Blindness, Repositório Científico do Instituto Politécnico do Porto, and Busch, Catharina
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Male ,Visual acuity ,genetic structures ,patient diabétique ,Endocrinology, Diabetes and Metabolism ,Visual Acuity ,Angiogenesis Inhibitors ,Observation ,oedème maculaire ,030204 cardiovascular system & hematology ,Cohort Studies ,0302 clinical medicine ,Endocrinology ,Good visual acuity ,Diabetic macular edema ,acuité visuelle ,Real world outcomes ,General Medicine ,Middle Aged ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,Prognosis ,Bevacizumab ,Treatment Outcome ,Intravitreal Injections ,Endocrinologie et métabolisme ,Female ,Original Article ,medicine.symptom ,Tomography, Optical Coherence ,Cohort study ,medicine.medical_specialty ,Vision Disorders ,Médecine humaine et pathologie ,030209 endocrinology & metabolism ,Macular Edema ,03 medical and health sciences ,Macular laser ,Ophthalmology ,Diabetes mellitus ,Internal Medicine ,medicine ,Humans ,Anti-VEGF therapy ,Aged ,Retrospective Studies ,Endocrinology and metabolism ,Diabetic Retinopathy ,Dose-Response Relationship, Drug ,business.industry ,Intravitreal therapy ,medicine.disease ,eye diseases ,laser ,Human health and pathology ,sense organs ,Subretinal fluid ,business ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology ,thérapie - Abstract
Aims To describe and compare the functional and anatomical outcomes of untreated and treated diabetic macular edema (DME) in eyes with very good baseline visual acuity (VA) in a real-world setting. Methods A 12-month, retrospective, multicenter, observational cohort study, including DME patients with baseline visual acuity (VA) ≤ 0.1 logMAR (≥ 20/25 Snellen) and central subfield thickness (CST) > 250 µm with intra- and/or subretinal fluid seen on optical coherence tomography. Results A total of 249 eyes were included, of which 155 were treated and 94 were non-treated during follow-up. Most eyes maintained vision (VA gain or VA loss
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- 2019
10. Linking YAP to Müller Glia Quiescence Exit in the Degenerative Retina
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Deniz Dalkara, Muriel Perron, Juliette Bitard, Jerome E. Roger, Annaïg Hamon, Diana García-García, Albert Chesneau, Divya Ail, Morgane Locker, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), Institut de la Vision, Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), PERRON, Muriel, and Gestionnaire, Hal Sorbonne Université
- Subjects
0301 basic medicine ,Transcription, Genetic ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV]Life Sciences [q-bio] ,Hippo/YAP pathway ,Cell Cycle Proteins ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,Xenopus Proteins ,Photoreceptor cell ,Xenopus laevis ,0302 clinical medicine ,lcsh:QH301-705.5 ,Retinal regeneration ,Mice, Knockout ,Cell Cycle ,Retinal Degeneration ,Cell biology ,Up-Regulation ,[SDV] Life Sciences [q-bio] ,medicine.anatomical_structure ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Reprogramming ,Muller glia ,Neuroglia ,Photoreceptor Cells, Vertebrate ,Signal Transduction ,Ependymoglial Cells ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Retina ,03 medical and health sciences ,reactive gliosis ,Downregulation and upregulation ,[SDV.BC.BC] Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,medicine ,Animals ,Humans ,EGFR pathway ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,retinal regeneration ,Adaptor Proteins, Signal Transducing ,Cell Proliferation ,Müller cells ,Hippo signaling pathway ,Epidermal Growth Factor ,Regeneration (biology) ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,YAP-Signaling Proteins ,Mice, Inbred C57BL ,030104 developmental biology ,lcsh:Biology (General) ,Trans-Activators ,sense organs ,030217 neurology & neurosurgery - Abstract
Summary: Contrasting with fish or amphibian, retinal regeneration from Müller glia is largely limited in mammals. In our quest toward the identification of molecular cues that may boost their stemness potential, we investigated the involvement of the Hippo pathway effector YAP (Yes-associated protein), which is upregulated in Müller cells following retinal injury. Conditional Yap deletion in mouse Müller cells prevents cell-cycle gene upregulation that normally accompanies reactive gliosis upon photoreceptor cell death. We further show that, in Xenopus, a species endowed with efficient regenerative capacity, YAP is required for their injury-dependent proliferative response. In the mouse retina, where Müller cells do not spontaneously proliferate, YAP overactivation is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Müller cell proliferative response to injury and highlight a YAP-EGFR (epidermal growth factor receptor) axis by which Müller cells exit their quiescence state, a critical step toward regeneration. : While fish and amphibian Müller cells behave as retinal stem cells upon injury, their regenerative potential is limited in mammals. Hamon et al. show that YAP is required for their cell-cycle re-entry in Xenopus and is sufficient in mouse to awake them from quiescence and trigger their proliferative response. Keywords: Müller cells, reactive gliosis, retinal regeneration, Hippo/YAP pathway, EGFR pathway
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- 2018
11. Cone-rod homeobox CRX controls presynaptic active zone formation in photoreceptors of mammalian retina
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Robert N. Fariss, Soo-Young Kim, Koray Dogan Kaya, Juthaporn Assawachananont, Anand Swaroop, Jerome E. Roger, National Institutes of Health [Bethesda] (NIH), National Eye Institute [Bethesda, MD, États-Unis] (NEI), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, and Partenaires INRAE-Partenaires INRAE
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0301 basic medicine ,MESH: Signal Transduction ,genetic structures ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Leber Congenital Amaurosis ,Ribbon synapse ,Mice ,0302 clinical medicine ,MESH: Eye Proteins ,Retinal Rod Photoreceptor Cells ,MESH: Gene Expression Regulation, Developmental ,MESH: Leber Congenital Amaurosis ,MESH: Presynaptic Terminals ,MESH: Animals ,Rod cell ,MESH: Nerve Tissue Proteins ,Genetics (clinical) ,biology ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,MESH: Retina ,Gene Expression Regulation, Developmental ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Cell Differentiation ,General Medicine ,Cell biology ,medicine.anatomical_structure ,Retinal Cone Photoreceptor Cells ,General Article ,Presynaptic active zone ,Signal Transduction ,MESH: Cell Differentiation ,MESH: Mice, Transgenic ,MESH: Trans-Activators ,Presynaptic Terminals ,Mice, Transgenic ,Nerve Tissue Proteins ,Synaptic vesicle ,Retina ,03 medical and health sciences ,MESH: Gene Expression Profiling ,MESH: Homeodomain Proteins ,Genetics ,medicine ,Animals ,Active zone ,Eye Proteins ,Molecular Biology ,MESH: Mice ,MESH: Retinal Rod Photoreceptor Cells ,Homeodomain Proteins ,Gene Expression Profiling ,eye diseases ,Disease Models, Animal ,030104 developmental biology ,MESH: Retinal Cone Photoreceptor Cells ,biology.protein ,Trans-Activators ,Homeobox ,Pikachurin ,sense organs ,MESH: Disease Models, Animal ,030217 neurology & neurosurgery - Abstract
International audience; In the mammalian retina, rod and cone photoreceptors transmit the visual information to bipolar neurons through highly specialized ribbon synapses. We have limited understanding of regulatory pathways that guide morphogenesis and organization of photoreceptor presynaptic architecture in the developing retina. While neural retina leucine zipper (NRL) transcription factor determines rod cell fate and function, cone-rod homeobox (CRX) controls the expression of both rod- and cone-specific genes and is critical for terminal differentiation of photoreceptors. A comprehensive immunohistochemical evaluation of Crx-/- (null), CrxRip/+ and CrxRip/Rip (models of dominant congenital blindness) mouse retinas revealed abnormal photoreceptor synapses, with atypical ribbon shape, number and length. Integrated analysis of retinal transcriptomes of Crx-mutants with CRX- and NRL-ChIP-Seq data identified a subset of differentially expressed CRX target genes that encode presynaptic proteins associated with the cytomatrix active zone (CAZ) and synaptic vesicles. Immunohistochemistry of Crx-mutant retina validated aberrant expression of REEP6, PSD95, MPP4, UNC119, UNC13, RGS7 and RGS11, with some reduction in Ribeye and no significant change in immunostaining of RIMS1, RIMS2, Bassoon and Pikachurin. Our studies demonstrate that CRX controls the establishment of CAZ and anchoring of ribbons, but not the formation of ribbon itself, in photoreceptor presynaptic terminals.
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- 2018
12. Müller glial cell‐dependent regeneration of the neural retina: An overview across vertebrate model systems
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Jerome E. Roger, Muriel Perron, Xian-Jie Yang, Annaïg Hamon, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Jules Stein Eye Institute University of California at Los Angeles, University of California [Los Angeles] (UCLA), and University of California-University of California-Jules Stein Eye Institute
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0301 basic medicine ,retina ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Ependymoglial Cells ,Reviews ,Context (language use) ,Biology ,Regenerative medicine ,03 medical and health sciences ,stem cells ,Animals ,Humans ,Progenitor cell ,Müller cells ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,Regeneration (biology) ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Anatomy ,3. Good health ,Transplantation ,030104 developmental biology ,regeneration ,Stem cell ,Reprogramming ,Neuroscience ,Retinal Dystrophies ,Developmental Biology - Abstract
Retinal dystrophies are a major cause of blindness for which there are currently no curative treatments. Transplantation of stem cell‐derived neuronal progenitors to replace lost cells has been widely investigated as a therapeutic option. Another promising strategy would be to trigger self‐repair mechanisms in patients, through the recruitment of endogenous cells with stemness properties. Accumulating evidence in the past 15 year0s has revealed that several retinal cell types possess neurogenic potential, thus opening new avenues for regenerative medicine. Among them, Müller glial cells have been shown to be able to undergo a reprogramming process to re‐acquire a stem/progenitor state, allowing them to proliferate and generate new neurons for repair following retinal damages. Although Müller cell–dependent spontaneous regeneration is remarkable in some species such as the fish, it is extremely limited and ineffective in mammals. Understanding the cellular events and molecular mechanisms underlying Müller cell activities in species endowed with regenerative capacities could provide knowledge to unlock the restricted potential of their mammalian counterparts. In this context, the present review provides an overview of Müller cell responses to injury across vertebrate model systems and summarizes recent advances in this rapidly evolving field. Developmental Dynamics 245:727–738, 2016. © 2015 The Authors. Developmental Dynamics published by Wiley Periodicals, Inc., Key findings The present review provides an overview of Müller cell responses to injury across vertebrate model systems and summarizes recent advances in this rapidly evolving field.
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- 2016
13. Repopulating retinal microglia restore endogenous organization and function under CX3CL1-CX3CR1 regulation
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Adam Lazere, Mones Abu-Asab, Wai T. Wong, Haohua Qian, Jun Zhang, Xu Wang, Lian Zhao, Yikui Zhang, Jerome E. Roger, Robert N. Fariss, Wenxin Ma, National Eye Institute [Bethesda, MD, États-Unis] (NEI), National Institutes of Health [Bethesda] (NIH), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Institut des Neurosciences Paris-Saclay (NeuroPSI), and Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS)
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0301 basic medicine ,Aging ,Chemokine ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Immunology ,CX3C Chemokine Receptor 1 ,Mice, Transgenic ,Endogeny ,Retina ,03 medical and health sciences ,Cell Movement ,CX3CR1 ,medicine ,Animals ,10. No inequality ,CX3CL1 ,Research Articles ,Cell Proliferation ,Multidisciplinary ,biology ,Microglia ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,Chemokine CX3CL1 ,Calcium-Binding Proteins ,Microfilament Proteins ,SciAdv r-articles ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,eye diseases ,030104 developmental biology ,medicine.anatomical_structure ,biology.protein ,sense organs ,Signal transduction ,Neuroscience ,Homeostasis ,Signal Transduction ,Research Article - Abstract
Chemokine signaling via CX3CL1-CX3CR1 helps regulate homeostasis in the population of microglia in the adult mouse retina., Microglia have been discovered to undergo repopulation following ablation. However, the functionality of repopulated microglia and the mechanisms regulating microglia repopulation are unknown. We examined microglial homeostasis in the adult mouse retina, a specialized neural compartment containing regular arrays of microglia in discrete synaptic laminae that can be directly visualized. Using in vivo imaging and cell-fate mapping techniques, we discovered that repopulation originated from residual microglia proliferating in the central inner retina that subsequently spread by centrifugal migration to fully recapitulate pre-existing microglial distributions and morphologies. Repopulating cells fully restored microglial functions including constitutive “surveying” process movements, behavioral and physiological responses to retinal injury, and maintenance of synaptic structure and function. Microglial repopulation was regulated by CX3CL1-CX3CR1 signaling, slowing in CX3CR1 deficiency and accelerating with exogenous CX3CL1 administration. Microglial homeostasis following perturbation can fully recover microglial organization and function under the regulation of chemokine signaling between neurons and microglia.
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- 2018
14. Retinal Degeneration and Regeneration-Lessons From Fishes and Amphibians
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Ail, Divya, Perron, Muriel, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, and Partenaires INRAE-Partenaires INRAE
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Xenopus and Zebrafish Models for Pathobiology (W Goessling and A Zorn, Section Editors) ,Retinal regeneration ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,Retinal stem cells ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Ciliary marginal zone ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Müller glial cells ,Retinal degeneration ,Retinal pigment epithelium - Abstract
Purpose of Review Retinal degenerative diseases have immense socio-economic impact. Studying animal models that recapitulate human eye pathologies aids in understanding the pathogenesis of diseases and allows for the discovery of novel therapeutic strategies. Some non-mammalian species are known to have remarkable regenerative abilities and may provide the basis to develop strategies to stimulate self-repair in patients suffering from these retinal diseases. Recent Findings Non-mammalian organisms, such as zebrafish and Xenopus, have become attractive model systems to study retinal diseases. Additionally, many fish and amphibian models of retinal cell ablation and cell lineage analysis have been developed to study regeneration. These investigations highlighted several cellular sources for retinal repair in different fish and amphibian species. Moreover, major differences in repair mechanisms have been reported in these animal models. Summary This review aims to emphasize first on the importance of zebrafish and Xenopus models in studying the pathogenesis of retinal diseases and, second, on the different modes of regeneration processes in these model organisms.
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- 2017
15. Redox equilibrium and retinal stem cell proliferation
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Lainé, Anaïs, Perron, Muriel, Locker, Morgane, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, and Lainé, Anaïs
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[SDV] Life Sciences [q-bio] ,[SDV]Life Sciences [q-bio] ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,ComputingMilieux_MISCELLANEOUS - Abstract
International audience
- Published
- 2016
16. IFT81, encoding an IFT-B core protein, as a very rare cause of a ciliopathy phenotype
- Author
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Josseline Kaplan, Tania Attié-Bitach, Meriem Garfa-Traore, Michael Taschner, Esben Lorentzen, Catherine Caillaud, Markus Schueler, Hanan M. Fathy, Xavier Gérard, Valérie Cormier-Daire, Heon Yung Gee, Nathalie Boddaert, Richard P. Lifton, Jonathan D. Porath, Jennifer A. Lawson, Jan Halbritter, Daniela A. Braun, Sophie Saunier, Friedhelm Hildebrandt, Philippe Bastin, Sophie Thomas, Edgar A. Otto, Jean-Michel Rozet, Isabelle Perrault, Imagine - Institut des maladies génétiques ( IMAGINE - U1163 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Division of Nephrology, Boston Children's Hospital, University Clinic, Leipzig, Pediatric Nephrology Unit, University of Alexandria, Service de Radiologie et imagerie médicale [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Max Planck Institute for Biochemistry, Max-Planck-Institut, Yale School of Medicine, University of Michigan [Ann Arbor], Biologie Cellulaire des Trypanosomes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), CHU Necker - Enfants Malades [AP-HP], Howard Hughes Medical Institute [Chevy Chase] ( HHMI ), Howard Hugues Medical Institute, This work was further supported by grants from the following funding agencies: the National Institutes of Health (NIH) to FH (DK068308), the ‘Agence Nationale de la Recherche’ (ANR) to SS and TA (20100BLAN112202, ANR-10-IAHY-01), the ‘Fondation pour la Recherche Médicale’ to SS (DEQ20130326532), the ‘Institut National de la Santé et de la Recherche Médicale’ (INSERM), the ‘Imagine Institute’, the ‘Association Retina France’ and PHRC GENPHENACL to JMR and JK. FH is an Investigator of the Howard Hughes Medical Institute (HHMI) and a Warren E Grupe Professor. The authors declare that they have no competing financial interests., ANR : IAHY, ANR-10-IAHY-01, Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Alexandria University [Alexandrie], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Max-Planck-Institut für Biochemie = Max Planck Institute of Biochemistry (MPIB), Max-Planck-Gesellschaft, Yale School of Medicine [New Haven, Connecticut] (YSM), University of Michigan System, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Howard Hughes Medical Institute [Chevy Chase] (HHMI), Howard Hughes Medical Institute (HHMI), ANR-10-IAHU-0001,Imagine,Institut Hospitalo-Universitaire Imagine(2010), Lassailly-Bondaz, Anne, Instituts Hospitalo-Universitaires - Institut Hospitalo-Universitaire Imagine - - Imagine2010 - ANR-10-IAHU-0001 - IAHU - VALID, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Max Planck Institute of Biochemistry (MPIB), Yale University School of Medicine, and Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS)
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Candidate gene ,Muscle Proteins ,Biology ,medicine.disease_cause ,Eye ,Kidney ,Ciliopathies ,Intraflagellar transport ,Nephronophthisis ,[ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology ,GLI2 ,medicine ,Genetics ,Humans ,Molecular genetics ,Cilia ,[SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology ,Genetics (clinical) ,Mutation ,Renal Medicine ,Cilium ,New Loci ,Sequence Analysis, DNA ,medicine.disease ,Ciliopathy ,Ophthalmology ,[SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology ,sense organs - Abstract
International audience; Background Bidirectional intraflagellar transport (IFT) consists of two major protein complexes, IFT-A and IFT-B. In contrast to the IFT-B complex, all components of IFT-A have recently been linked to human ciliopathies when defective. We therefore hypothesised that mutations in additional IFT-B encoding genes can be found in patients with multisystemic ciliopathies. Methods We screened 1628 individuals with renoocular ciliopathies by targeted next-generation sequencing of ciliary candidate genes, including all IFT-B encoding genes. Results Consequently, we identified a homozygous mutation in IFT81 affecting an obligatory donor splice site in an individual with nephronophthisis and polydactyly. Further, we detected a loss-of-stop mutation with extension of the deduced protein by 10 amino acids in an individual with neuronal ceroid lipofuscinosis-1. This proband presented with retinal dystrophy and brain lesions including cerebellar atrophy, a phenotype to which the IFT81 variant might contribute. Cultured fibroblasts of this latter affected individual showed a significant decrease in ciliated cell abundance compared with controls and increased expression of the transcription factor GLI2 suggesting deranged sonic hedgehog signalling. Conclusions This work describes identification of mutations of IFT81 in individuals with symptoms consistent with the clinical spectrum of ciliopathies. It might represent the rare case of a core IFT-B complex protein found associated with human disease. Our data further suggest that defects in the IFT-B core are an exceedingly rare finding, probably due to its indispensable role for ciliary assembly in development.
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- 2015
17. An atlas of Wnt activity during embryogenesis in Xenopus tropicalis
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Caroline Borday, Hong Thi Tran, Karine Parain, Anne-Hélène Monsoro-Burq, Kris Vleminckx, Muriel Perron, Signalisation normale et pathologique de l'embryon aux thérapies innovantes des cancers, Institut Curie [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Department of Biomedical Molecular Biology [Ghent], Universiteit Gent = Ghent University [Belgium] (UGENT), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, and Partenaires INRAE-Partenaires INRAE
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0301 basic medicine ,Embryology ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Xenopus ,lcsh:Medicine ,Xenopus Proteins ,BETA-CATENIN ,OPTIC CUP ,Cell Signaling ,Neural Stem Cells ,Animal Cells ,Medicine and Health Sciences ,lcsh:Science ,Wnt Signaling Pathway ,Zebrafish ,WNT Signaling Cascade ,In Situ Hybridization ,Multidisciplinary ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,Stem Cells ,Wnt signaling pathway ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,Eukaryota ,Gene Expression Regulation, Developmental ,Neural crest ,Animal Models ,Signaling Cascades ,Cell biology ,Cell Motility ,medicine.anatomical_structure ,Experimental Organism Systems ,Neural Crest ,SIGNALING ,Vertebrates ,Frogs ,Cellular Types ,Cellular Structures and Organelles ,CYCLIN D1 GENE ,STEM-CELLS ,Research Article ,Signal Transduction ,EXPRESSION ,Neural Tube ,Beta-catenin ,Molecular Probe Techniques ,Embryonic Development ,Cell Migration ,Biology ,Research and Analysis Methods ,Amphibians ,03 medical and health sciences ,Model Organisms ,Developmental Neuroscience ,NEURAL CREST INDUCTION ,medicine ,Animals ,Vesicles ,Molecular Biology Techniques ,Molecular Biology ,CILIARY MARGIN ,ZEBRAFISH ,Embryos ,lcsh:R ,Embryogenesis ,Organisms ,Neural tube ,Biology and Life Sciences ,PATHWAYS ,Cell Biology ,Gastrula ,biology.organism_classification ,Probe Hybridization ,Wnt Proteins ,Gastrulation ,PLATE BORDER ,030104 developmental biology ,Cellular Neuroscience ,biology.protein ,lcsh:Q ,Developmental Biology ,Neuroscience - Abstract
International audience; Wnt proteins form a family of highly conserved secreted molecules that are critical mediators of cell-cell signaling during embryogenesis. Partial data on Wnt activity in different tissues and at different stages have been reported in frog embryos. Our objective here is to provide a coherent and detailed description of Wnt activity throughout embryo development. Using a transgenic Xenopus tropicalis line carrying a Wnt-responsive reporter sequence, we depict the spatial and temporal dynamics of canonical Wnt activity during embryogenesis. We provide a comprehensive series of in situ hybridization in whole-mount embryos and in cross-sections, from gastrula to tadpole stages, with special focus on neural tube, retina and neural crest cell development. This collection of patterns will thus constitute a valuable resource for developmental biologists to picture the dynamics of Wnt activity during development.
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- 2018
18. YAP controls retinal stem cell DNA replication timing and genomic stability
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Juliette Bitard, Christel Masson, Karine Parain, Kristine A. Henningfeld, Odile Bronchain, Marie Hedderich, Romain Chemouny, Muriel Perron, Guillermo A. Vega-Lopez, Morgane Locker, Pauline Cabochette, Caroline Borday, Institut des Neurosciences Paris-Saclay (NeuroPSI), Université Paris-Sud - Paris 11 (UP11)-Centre National de la Recherche Scientifique (CNRS), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, and Center for Nanoscale Microscopy and Molecular Physiology of the Brain
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Genome instability ,retina ,Cell division ,DNA Replication Timing ,QH301-705.5 ,DNA damage ,Xenopus ,Science ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,YAP ,DNA ,genomic stability ,Xenopus Proteins ,Biology ,Genomic Instability ,General Biochemistry, Genetics and Molecular Biology ,neural stem cell ,ciliary marginal zone ,Animals ,Biology (General) ,neural stem cells ,Genetics ,Hippo signaling pathway ,General Immunology and Microbiology ,[SDV.NEU.PC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Psychology and behavior ,Stem Cells ,General Neuroscience ,DNA replication ,[SDV.NEU.SC]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Cognitive Sciences ,YAP-Signaling Proteins ,General Medicine ,Neural stem cell ,Cell biology ,Developmental Biology and Stem Cells ,cell proliferation ,Hippo/Yap pathway ,Trans-Activators ,Medicine ,Stem cell ,Cell Division ,Research Article - Abstract
The adult frog retina retains a reservoir of active neural stem cells that contribute to continuous eye growth throughout life. We found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in these stem cells. Yap knock-down leads to an accelerated S-phase and an abnormal progression of DNA replication, a phenotype likely mediated by upregulation of c-Myc. This is associated with an increased occurrence of DNA damage and eventually p53-p21 pathway-mediated cell death. Finally, we identified PKNOX1, a transcription factor involved in the maintenance of genomic stability, as a functional and physical interactant of YAP. Altogether, we propose that YAP is required in adult retinal stem cells to regulate the temporal firing of replication origins and quality control of replicated DNA. Our data reinforce the view that specific mechanisms dedicated to S-phase control are at work in stem cells to protect them from genomic instability. DOI: http://dx.doi.org/10.7554/eLife.08488.001, eLife digest In animals, stem cells divide to produce the new cells needed to grow and renew tissues and organs. Understanding the biology of these cells is of the utmost importance for developing new treatments for a wide range of human diseases, including neurodegenerative diseases and cancer. Before a stem cell divides, it copies its DNA and the two sets of genetic instructions are then separated so that the two daughter cells both have a complete set. This process needs to be as accurate as possible because any errors would result in incorrect genetic information being passed on to the daughter cells. Stem cells in the light-sensitive part of the eye—called the retina—divide to produce the cells that detect light and relay visual information to the brain. In many animals, these stem cells stop dividing soon after birth and the retina stops growing. However, the stem cells in frogs and fish continue to divide throughout the life of the animal, which enables the eye to keep on growing. A protein called YAP regulates the growth of organs in animal embryos, but it is not clear what role this protein plays in stem cells, particularly after birth. To address this question, Cabochette et al. studied YAP in the retina of frog tadpoles. The experiments show that YAP is produced in the stem cells of the retina after birth and is required for the retina to continue to grow. Cabochette et al. used tools called ‘photo-cleavable Morpholinos’ to alter the production of YAP in adult stem cells. The cells that produced less YAP copied their DNA more quickly and more of their DNA became damaged, which eventually led to the death of these cells. Further experiments revealed that YAP interacts with a protein called PKNOX1, which is involved in maintaining the integrity of DNA. Cabochette et al.'s findings provide the first insights into how YAP works in the stem cells of the retina and demonstrate that it plays a crucial role in regulating when DNA is copied. A future challenge is to find out whether YAP plays a similar role in the stem cells of other organs in adult animals. DOI: http://dx.doi.org/10.7554/eLife.08488.002
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- 2015
19. A missense mutation in melanocortin 1 receptor is associated with the red coat colour in donkeys
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Laurent Tiret, Marie Abitbol, Romain Legrand, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, and Partenaires INRAE-Partenaires INRAE
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miniature donkey ,Coat ,melanocyte ,Genotype ,chestnut ,melanocortin 1 receptor ,Normand donkey ,[SDV]Life Sciences [q-bio] ,Mutation, Missense ,Genes, Recessive ,Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Genetics ,Animals ,Missense mutation ,Allele ,Hair Color ,Gene ,Alleles ,030304 developmental biology ,0303 health sciences ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Methionine ,0402 animal and dairy science ,Equidae ,04 agricultural and veterinary sciences ,General Medicine ,040201 dairy & animal science ,[SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics ,chemistry ,Animal Science and Zoology ,Donkey ,Melanocortin ,Receptor, Melanocortin, Type 1 ,Melanocortin 1 receptor - Abstract
International audience; The seven donkey breeds recognised by the French studbook are characterised by few coat colours: black, bay and grey. Normand bay donkeys seldom give birth to red foals, a colour more commonly seen and recognised in American miniature donkeys. Red resembles the equine chestnut colour, previously attributed to a mutation in the melanocortin 1 receptor gene (MC1R). We used a panel of 124 donkeys to identify a recessive missense c.629T>C variant in MC1R that showed a perfect association with the red coat colour. This variant leads to a methionine to threonine substitution at position 210 in the protein. We showed that methionine 210 is highly conserved among vertebrate melanocortin receptors. Previous in silico and in vitro analyses predicted this residue to lie within a functional site. Our in vivo results emphasised the pivotal role played by this residue, the alteration of which yielded a phenotype fully compatible with a loss of function of MC1R. We thus propose to name the c.629T>C allele in donkeys the e allele, which further enlarges the panel of recessive MC1R loss-of-function alleles described in animals and humans.
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- 2014
20. Homozygous Deletion in the Coding Sequence of the c-mer Gene in RCS Rats Unravels General Mechanisms of Physiological Cell Adhesion and Apoptosis
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Jean-Louis Dufier, Maurice Menasche, Cécile Marsac, Eric M Dufour, Alexandra C. Provost, Marie-Thérèse Bihoreau, Sébastien Bonnel, Bertille Sépulchre de Condé, Christelle Rouillac, Cindi Shaver, Karïn Gogat, Emeline F. Nandrot, Marie O. Pequignot, Mark Lathrop, Marc Abitbol, Dominique Marchant, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford, Genoscope - Centre national de séquençage [Evry] (GENOSCOPE), Université Paris-Saclay-Direction de Recherche Fondamentale (CEA) (DRF (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Nandrot, Emeline, and University of Oxford [Oxford]
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Candidate gene ,retinal pigment epithelium ,Receptor tyrosine kinase ,0302 clinical medicine ,Rats, Inbred BN ,Coding region ,Inbreeding ,Fluorescein Angiography ,Peptide sequence ,Sequence Deletion ,0303 health sciences ,biology ,Homozygote ,apoptosis ,Chromosome Mapping ,phagocytosis ,Protein-Tyrosine Kinases ,macrophages ,Phenotype ,Neurology ,Organ Specificity ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,RCS rats ,Genotype ,Molecular Sequence Data ,Genes, Recessive ,Locus (genetics) ,Rats, Mutant Strains ,lcsh:RC321-571 ,03 medical and health sciences ,Retinal Diseases ,Proto-Oncogene Proteins ,Cell Adhesion ,Electroretinography ,Animals ,Radiation hybrid mapping ,Amino Acid Sequence ,RNA, Messenger ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,Gene ,Crosses, Genetic ,030304 developmental biology ,Base Sequence ,c-Mer Tyrosine Kinase ,GAS6 ,Receptor Protein-Tyrosine Kinases ,Sequence Analysis, DNA ,Molecular biology ,Rats ,c-mer ,biology.protein ,030217 neurology & neurosurgery - Abstract
International audience; The RCS rat presents an autosomal recessive retinal pigment epithelium dystrophy characterized by the outer segments of photoreceptors being phagocytosis-deficient. A systematic genetic study allowed us to restrict the interval containing the rdy locus to that between the markers D3Mit13 and D3Rat256. We report the chromosomal localization of the rat c-mer gene in the cytogenetic bands 3q35-36, based on genetic analysis and radiation hybrid mapping. Using a systematic biocomputing analysis, we identified two strong related candidate genes encoding protein tyrosine kinase receptors of the AXL subfamily. The comparison of their expression patterns in human and mice tissues suggested that the c-mer gene was the best gene to screen for mutations. RCS rdy؊ and RCS rdy؉ cDNAs were sequenced. The RCS rdy؊ cDNAs carried a significant deletion in the 5 part of the coding sequence of the c-mer gene resulting in a shortened aberrant transcript encoding a 20 amino acid peptide. The c-mer gene contains characteristic motifs of neural cell adhesion. A ligand of the c-mer receptor, Gas6, exhibits antiapoptotic properties.
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- 2000
21. Le rôle des lipides dans les maladies de l’œil
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Brétillon, Lionel, Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Centre National de la Recherche Scientifique (CNRS)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB), Association RETINA France., ProdInra, Archive Ouverte, Centre des Sciences du Goût et de l'Alimentation [Dijon] ( CSGA ), Institut National de la Recherche Agronomique ( INRA ) -Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique ( CNRS ), and Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)
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alimentation ,[ SDV.AEN ] Life Sciences [q-bio]/Food and Nutrition ,rétine ,dmla ,oméga 3 ,vieillissement ,prévention ,[SDV.AEN] Life Sciences [q-bio]/Food and Nutrition ,pathologie ,lipide ,Alimentation et Nutrition ,Food and Nutrition ,[SDV.AEN]Life Sciences [q-bio]/Food and Nutrition - Abstract
Le rôle des lipides dans les maladies de l’œil
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- 2012
22. A canine Arylsulfatase G (ARSG) mutation leading to a sulfatase deficiency is associated with neuronal ceroid lipofuscinosis
- Author
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Françoise Gray, Natasha J. Olby, Sandra Brahimi, Jean-Laurent Thibaud, Fanny Pilot-Storck, Marie Abitbol, Benoit Hedan, Catherine Caillaud, Jean-Philippe Puech, Marie Maurer, Stéphane Dréano, Christophe Hitte, Delphine Delattre, Françoise Delisle, Laurent Tiret, Stéphane Blot, Catherine André, Geneviève Aubin-Houzelstein, Jean-Jacques Panthier, Florence Bernex, Génétique Moléculaire et Cellulaire (UGMC), École nationale vétérinaire - Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Laboratoire de neurobiologie, École nationale vétérinaire - Alfort (ENVA), Department of Clinical Sciences, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), Institut de Génétique et Développement de Rennes (IGDR), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de biochimie et génétique moléculaire, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Descartes - Paris 5 (UPD5), Antagene, Service d'anatomie et cytologie pathologiques, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Centre de radiothérapie-Scanner, De Villemeur, Hervé, École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), École nationale vétérinaire d'Alfort (ENVA), Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, MICEN-Vet, Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique )-Centre National de la Recherche Scientifique (CNRS)-Université de Rennes 1 (UR1), Ecole Natl Vet Alfort, Fonctions et dysfonctions épithéliales - UFC (EA 4267) (FDE), Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Alcatel-Thales III-V Lab (III-V Lab), THALES, Génétique fonctionnelle et médicale (GFM - ENVA), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-IFR140-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 (UPD5), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Génétique Moléculaire et Cellulaire ( UGMC ), Institut National de la Recherche Agronomique ( INRA ) -Ecole Nationale Vétérinaire d'Alfort, Ecole Nationale Vétérinaire d'Alfort, North Carolina State University [Raleigh] ( NCSU ), Institut de Génétique et Développement de Rennes ( IGDR ), Université de Rennes 1 ( UR1 ), Université de Rennes ( UNIV-RENNES ) -Université de Rennes ( UNIV-RENNES ) -IFR140-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Cochin [AP-HP]-Université Paris Descartes - Paris 5 ( UPD5 ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 ( UPD7 ), CERTO, sans affiliation, Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Université de Rennes (UR)-Centre National de la Recherche Scientifique (CNRS)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and THALES [France]
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Male ,Candidate gene ,[SDV]Life Sciences [q-bio] ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,0403 veterinary science ,Gene Frequency ,Catalytic Domain ,Missense mutation ,Dog Diseases ,ComputingMilieux_MISCELLANEOUS ,Arylsulfatases ,Genetics ,0303 health sciences ,Multidisciplinary ,Reverse Transcriptase Polymerase Chain Reaction ,Sulfatase ,Age Factors ,Chromosome Mapping ,04 agricultural and veterinary sciences ,Biological Sciences ,3. Good health ,Pedigree ,Cerebellar cortex ,dog ,lysosome ,Female ,[SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,Genotype ,040301 veterinary sciences ,Molecular Sequence Data ,Mutation, Missense ,Locus (genetics) ,Biology ,Polymorphism, Single Nucleotide ,Cell Line ,03 medical and health sciences ,Cerebellar Cortex ,Dogs ,Microscopy, Electron, Transmission ,Neuronal Ceroid-Lipofuscinoses ,medicine ,Animals ,Humans ,[SDV.NEU] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Genetic heterogeneity ,Gene Expression Profiling ,animal model ,Haplotype ,ataxia ,medicine.disease ,Molecular biology ,Chromosomes, Mammalian ,Haplotypes ,[ SDV.NEU ] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC] ,neurodegenerative ,Neuronal ceroid lipofuscinosis ,ATP-Binding Cassette Transporters ,[ SDV.GEN ] Life Sciences [q-bio]/Genetics ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
Neuronal ceroid lipofuscinoses (NCLs) represent the most common group of inherited progressive encephalopathies in children. They are characterized by progressive loss of vision, mental and motor deterioration, epileptic seizures, and premature death. Rare adult forms of NCL with late onset are known as Kufs’ disease. Loci underlying these adult forms remain unknown due to the small number of patients and genetic heterogeneity. Here we confirm that a late-onset form of NCL recessively segregates in US and French pedigrees of American Staffordshire Terrier (AST) dogs. Through combined association, linkage, and haplotype analyses, we mapped the disease locus to a single region of canine chromosome 9. We eventually identified a worldwide breed-specific variant in exon 2 of the Arylsulfatase G ( ARSG ) gene, which causes a p.R99H substitution in the vicinity of the catalytic domain of the enzyme. In transfected cells or leukocytes from affected dogs, the missense change leads to a 75% decrease in sulfatase activity, providing a functional confirmation that the variant might be the NCL-causing mutation. Our results uncover a protein involved in neuronal homeostasis, identify a family of candidate genes to be screened in patients with Kufs' disease, and suggest that a deficiency in sulfatase is part of the NCL pathogenesis.
- Published
- 2010
23. Prospective echocardiographic and tissue Doppler imaging screening of a population of Maine Coon cats tested for the A31P mutation in the myosin-binding protein C gene: a specific analysis of the heterozygous status
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Renaud Tissier, J. Mary, François Serres, J.-L. Pouchelon, Valérie Chetboul, Vassiliki Gouni, Marie Abitbol, Anne Thomas, C. Carlos Sampedrano, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Laboratoire pour l'utilisation des lasers intenses (LULI), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-École polytechnique (X)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), INL - Photovoltaïque (INL - PV), Institut des Nanotechnologies de Lyon (INL), Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-École Centrale de Lyon (ECL), Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE)-Centre National de la Recherche Scientifique (CNRS)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-École supérieure de Chimie Physique Electronique de Lyon (CPE), École Centrale de Lyon (ECL), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-École Supérieure de Chimie Physique Électronique de Lyon (CPE)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)-École Centrale de Lyon (ECL), and Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Centre National de la Recherche Scientifique (CNRS)
- Subjects
Male ,medicine.medical_specialty ,Pathology ,040301 veterinary sciences ,genotype ,[SDV]Life Sciences [q-bio] ,Population ,Cardiomyopathy ,Diastole ,Loss of Heterozygosity ,030204 cardiovascular system & hematology ,Left ventricular hypertrophy ,Cat Diseases ,Muscle hypertrophy ,0403 veterinary science ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,medicine ,Animals ,Genetic Predisposition to Disease ,Interventricular septum ,cardiovascular diseases ,feline ,education ,education.field_of_study ,CATS ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,General Veterinary ,business.industry ,[SDV.BA]Life Sciences [q-bio]/Animal biology ,Homozygote ,Hypertrophic cardiomyopathy ,04 agricultural and veterinary sciences ,Cardiomyopathy, Hypertrophic ,medicine.disease ,medicine.anatomical_structure ,Endocrinology ,Gene Expression Regulation ,Echocardiography ,Mutation ,Cats ,Female ,business ,Carrier Proteins ,cardiomyopathy - Abstract
Chantier qualité GA; International audience; Background: A mutation in the sarcomeric gene coding for the myosin-binding protein C gene has been identified in a colony of Maine Coon cats with hypertrophic cardiomyopathy (MyBPC3-A31P mutation). However, the close correlation between genotype and phenotype (left ventricular hypertrophy [LVH] and dysfunction) has never been assessed in a large population, particularly in heterozygous (Hetero) cats. Objectives: To investigate LV morphology and function with echocardiography and tissue Doppler imaging (TDI) in a population of Maine Coon cats tested for the MyBPC3-A31P mutation with focus on Hetero animals. Animals: Ninety-six Maine Coon cats. Methods: Prospective observational study. Cats were screened for the MyBPC3-A31P mutation and examined with both echocardiography and 2-dimensional color TDI. Results: Fifty-two out of 96 cats did not have the mutation (wild-type genotype, Homo WT), 38/96 and 6/96 were Hetero- and homozygous-mutated (Homo M) cats, respectively. Only 11% of Hetero cats (4/38) had LVH and 29% (10/34) of Hetero cats without LVH were >4 years old (4.1–11.5 years). LVH was also detected in 2 Homo WT cats (4%). A significantly decreased (P < .05) longitudinal E/A (ratio between early and late diastolic myocardial velocities) in the basal segment of the interventricular septum was observed in Hetero cats without LVH (n = 34) compared with Homo WT cats without LVH (n = 50), thus confirming that the Hetero status is associated with regional diastolic dysfunction (P < .05). Conclusions: The heterozygous status is not consistently associated with LVH and major myocardial dysfunction. Moreover, Homo WT cats can also develop LVH, suggesting that other genetic causes might be implicated.
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- 2009
24. Biomarkers of inflammation and malnutrition associated with early death in healthy elderly people
- Author
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Carriere, Isabelle, Dupuy, Anne-Marie, Lacroux, Annie, Cristol, Jean-Paul, Delcourt, Cécile, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Equipe associée, Université Montpellier 1 (UM1), Épidémiologie et prévention : environnement et efficacité des interventions (EPIPREV), Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Fondation de France, Fondation pour la recherche Médicale, Région Languedoc-Roussillon, Association Retina France, Rhones Poulenc, Essilor, Specia, Horiba ABX Montpellier, Centre de Recherche et d'Information Nutritionnelle, Villebrun, Dominique, and Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)
- Subjects
Male ,MESH: Risk Assessment ,MESH: Proportional Hazards Models ,MESH: Cause of Death ,MESH: Health Surveys ,MESH: Aged, 80 and over ,MESH: Cholesterol ,Reference Values ,Cause of Death ,Neoplasms ,Prealbumin ,MESH: Neoplasms ,Prospective Studies ,Aged, 80 and over ,MESH: Aged ,MESH: Middle Aged ,[SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,[SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,Age Factors ,MESH: Reference Values ,Orosomucoid ,MESH: Follow-Up Studies ,Middle Aged ,C-Reactive Protein ,Cholesterol ,Cardiovascular Diseases ,MESH: Orosomucoid ,Female ,France ,Inflammation Mediators ,MESH: Inflammation Mediators ,MESH: Serum Albumin ,Protein-Energy Malnutrition ,Risk Assessment ,Article ,Sex Factors ,MESH: Sex Factors ,MESH: Prealbumin ,MESH: C-Reactive Protein ,Humans ,Serum Albumin ,Aged ,Proportional Hazards Models ,MESH: Age Factors ,MESH: Humans ,MESH: Cardiovascular Diseases ,Health Surveys ,MESH: Male ,MESH: Prospective Studies ,MESH: Protein-Energy Malnutrition ,MESH: France ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,MESH: Female ,Follow-Up Studies - Abstract
International audience; OBJECTIVES: To determine whether malnutrition and biomarkers of inflammation predict all-cause, cancer, and cardiovascular mortality in healthy elderly subjects. DESIGN: Population-based study, prospective cohort. SETTING: S?, on the French Mediterranean coast. PARTICIPANTS: Five hundred and fifty-three men and 888 women aged 60 and older from the Pathologies Oculaires Li? ?'Age cohort free of known comorbidities. MEASUREMENTS: Plasma levels of cholesterol, albumin, transthyretin (TTR), C-reactive protein (CRP), and alpha 1-acid glycoprotein (AAG) were measured at baseline. To investigate the risks of 5-year (early) and 5- to 9-year (late) mortality, hazard ratios (HR) were evaluated using Cox models. RESULTS: In men, early death was associated with high CRP and AAG and low albumin and TTR. In women, early death was associated with high AAG, low TTR and low cholesterol. For late death, the only significant association was with CRP in men. A synergistic effect was observed between biomarkers of inflammation and malnutrition. In men, the adjusted HR of early death was 4.98 (95% confidence interval (CI)=2.25-11.01) for both CRP in the highest quartile and albumin in the lowest. In men, this risk was greatest for both AAG in the highest quartile and TTR in the lowest (HR=6.86, 95% CI=3.20-14.71). In women, this risk was greatest for both AAG in the highest quartile and TTR in the lowest (HR=4.64, 95% CI=1.79-12.05). Cancer mortality was greater for high CRP and AAG and for low albumin and TTR in men but not in women. CONCLUSION: Biomarkers of inflammation and malnutrition together predict early mortality. In healthy elderly subjects, TTR and AAG could be helpful in identifying elderly subjects at higher risk of death.
- Published
- 2008
25. Waist Circumference Adds to the Variance in Plasma C-Reactive Protein Levels in Elderly Patients with Metabolic Syndrome
- Author
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Dupuy, Anne-Marie, Jaussent, Isabelle, Lacroux, Annie, Durant, Richard, Cristol, Jean-Paul, Delcourt, Cécile, Study Group, Pola, Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Épidémiologie et prévention : environnement et efficacité des interventions (EPIPREV), Département de Gériatrie, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, INSERM,Fondation de France, Department of Epidemiology of Ageing, Paris, the Fondation pour la Recherche Médicale, Paris, the Région Languedoc-Roussillon, Montpellier, France and the Association Retina-France, Toulouse, Rhônes Poulenc, Essilor and Specia, and the Centre de Recherche et d'Information Nutritionnelle, Paris., and Villebrun, Dominique
- Subjects
Male ,Aging ,medicine.medical_specialty ,Chronic bronchitis ,Waist ,Population ,Blood Pressure ,Disease ,Sex Factors ,Elderly ,Internal medicine ,Diabetes mellitus ,medicine ,Humans ,education ,National Cholesterol Education Program ,Triglycerides ,Aged ,Metabolic Syndrome ,Inflammation ,[SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,education.field_of_study ,biology ,[SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,Waist-Hip Ratio ,business.industry ,[SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,Cholesterol, HDL ,Smoking ,C-reactive protein ,Middle Aged ,[SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism ,medicine.disease ,Atherosclerosis ,C-Reactive Protein ,Endocrinology ,Adipose Tissue ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Multivariate Analysis ,biology.protein ,Female ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,Geriatrics and Gerontology ,Metabolic syndrome ,business - Abstract
Background: C-reactive protein (CRP), a nonspecific marker of the inflammatory status, is associated with cardiovascular disease risk factors and may be an important feature of the metabolic syndrome (MSX) in middle-aged subjects. Objectives: We assessed the relationship of CRP levels to specific components of MSX and other potential determinants in apparently healthy elderly subjects living in the South of France. Methods: In the framework of the population-based POLA (Pathologies Oculaires Liées à l’Age) Study, performed in 2,404 subjects aged 60 years or more, we measured the plasma CRP levels. All subjects with known systemic inflammatory diseases, such as chronic bronchitis, cardiovascular disease, and diabetes, and those who were on systemic steroid therapy as well as subjects with CRP levels >10 mg/l were excluded from the study, leaving 1,709 subjects for the statistical analyses. MSX was defined according to NCEP (National Cholesterol Education Program) criteria. Other potential determinants were assessed through interviewer-based questionnaire. Results: We grouped the subjects into three categories based on the 75th and 25th percentiles, corresponding to 3.05 and 0.82, respectively. We compared subjects in the highest quartile, i.e., with CRP ≧3.05 mg/l, with those in the two intermediate quartiles, i.e., with 0.82 < CRP < 3.05, and those in the lowest quartile, i.e., with CRP Conclusions: Abdominal adiposity adds to the variance in plasma CRP levels in elderly patients with MSX. This suggests that weight loss or other interventions targeted at adipocyte-related inflammation may represent an important means to prevent subclinical inflammation in the elderly, bearing a high risk of cardiovascular disease.
- Published
- 2007
26. Retinal cell type expression specificity of HIV-1-derived gene transfer vectors upon subretinal injection in the adult rat: influence of pseudotyping and promoter
- Author
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Jacques Mallet, Sébastien Bonnel, Noelle Dufour, Marc Abitbol, Chamsy Sarkis, Alexis-Pierre Bemelmans, Dominique Helmlinger, Emeline F. Nandrot, Leïla Houhou, Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Centre d'étude et de recherche thérapeutiques en ophtalmologie, Université Paris Descartes - Paris 5 (UPD5), Centre de recherche en Biologie Cellulaire (CRBM), Université Montpellier 2 - Sciences et Techniques (UM2)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1), CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Toussaint, Jean-Luc, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)
- Subjects
MESH: Lyssavirus ,Genetic enhancement ,MESH: Photoreceptors, Vertebrate ,[SDV]Life Sciences [q-bio] ,retinal pigment epithelium ,[SDV.BBM.BM] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Green fluorescent protein ,MESH: HIV-1 ,0302 clinical medicine ,Viral Envelope Proteins ,MESH: Genetic Vectors ,Drug Discovery ,MESH: Animals ,Pigment Epithelium of Eye ,Promoter Regions, Genetic ,gene transfer ,Genetics (clinical) ,ComputingMilieux_MISCELLANEOUS ,0303 health sciences ,biology ,MESH: Retina ,photoreceptors ,3. Good health ,MESH: Promoter Regions (Genetics) ,medicine.anatomical_structure ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Vesicular stomatitis virus ,Pseudotyping ,Molecular Medicine ,Photoreceptor Cells, Vertebrate ,MESH: Rats ,MESH: Vesicular stomatitis-Indiana virus ,Transgene ,Genetic Vectors ,Green Fluorescent Proteins ,MESH: Pigment Epithelium of Eye ,Retina ,Vesicular stomatitis Indiana virus ,Injections ,Viral vector ,03 medical and health sciences ,MESH: Green Fluorescent Proteins ,Genetics ,medicine ,Animals ,MESH: Injections ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Molecular Biology ,pseudotyping ,030304 developmental biology ,Reporter gene ,Retinal pigment epithelium ,promoter ,lentiviral vector ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,biology.organism_classification ,Molecular biology ,Rats ,MESH: Viral Envelope Proteins ,HIV-1 ,Lyssavirus ,030217 neurology & neurosurgery - Abstract
Background Gene therapy, and particularly gene restoration, is currently a great hope for non-curable hereditary retinal degeneration. Clinical applications require a gene transfer vector capable of accurately targeting particular cell types in the retina. To develop such a vector, we compared the expression of a reporter gene after subretinal injections of lentiviral constructs of various pseudotypes and with the transgene expression driven by various promoters. Methods Lentiviral vectors expressing the green fluorescent protein (GFP) under the transcriptional control of cytomegalovirus (CMV), mouse phosphoglycerate kinase (PGK), human elongation factor 1-α (EF1α), or human rhodopsin (RHO) promoters were pseudotyped by vesicular stomatitis virus (VSV) or Mokola virus envelope proteins. These constructs were injected into the subretinal space of adult rdy rats. GFP expression was analyzed in vivo 1 and 4 weeks after injection by fundus examination. The precise location of transgene expression was then determined by immunohistochemistry and in situ hybridization. Results Constructs of both vesicular stomatitis virus and Mokola pseudotypes with ubiquitous promoters led to a strong expression of GFP in vivo. Histological studies confirmed the production of GFP in the retinal pigment epithelium (RPE) in most cases. However, only the combination of the VSV pseudotype with the RHO promoter led to GFP production in photoreceptors, and did so in a sporadic manner. Conclusions Mokola-pseudotyped lentiviral vectors are effective for specific gene transfer to the RPE. Neither VSV- nor Mokola-pseudotyped lentiviral vectors are adequate for efficient gene transfer to photoreceptors of adult rats. Copyright © 2005 John Wiley & Sons, Ltd.
- Published
- 2005
27. Identification of novel genes and altered signaling pathways in the retinal pigment epithelium during the Royal College of Surgeons rat retinal degeneration
- Author
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Deborah Carper, Stéphanie Gadin, Marc Abitbol, Cécile Marsac, Eric M Dufour, Dominique Marchant, Loïc Van Den Berghe, Jean-Louis Dufier, Emeline F. Nandrot, Moussa Issilame, Maurice Menasche, Nandrot, Emeline, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, and National Institutes of Health, National Eye Institute, Section on Molecular Therapeutics
- Subjects
Retinal degeneration ,DNA, Complementary ,Phagocytosis ,Molecular Sequence Data ,Retinoic acid ,Microarray ,Biology ,Endocytosis ,Rats, Mutant Strains ,lcsh:RC321-571 ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,medicine ,Animals ,RCS rat ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Pigment Epithelium of Eye ,Retinal pigment epithelium ,lcsh:Neurosciences. Biological psychiatry. Neuropsychiatry ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Oligonucleotide Array Sequence Analysis ,0303 health sciences ,Differential display ,Base Sequence ,Retinal Degeneration ,medicine.disease ,Rod Cell Outer Segment ,Cell biology ,Rats ,medicine.anatomical_structure ,Neurology ,Transcytosis ,chemistry ,Gene Expression Regulation ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Gene expression ,Signal transduction ,030217 neurology & neurosurgery ,Signal Transduction - Abstract
Shed photoreceptor outer segments (POS) are phagocytosed by RPE cells in a circadian manner. The homozygous deletion of the c-mer gene abolishes the ingestion phase of this phagocytosis in the Royal College of Surgeons (RCS) rat strain, which in turn leads to the death of photoreceptor cells. We identified RPE transcripts for which the expression is modulated by the abrogation of POS phagocytosis. A microarray approach and the differential display (DDRT–PCR) technique revealed 116 modulated known genes, 4 modulated unknown genes, and 15 expressed sequenced tags (ESTs) corresponding to unknown genes. The microarray and DDRT–PCR analyses detected alterations in signaling pathways such as the phosphatidylinositol 3-kinase–Akt–mTOR pathway and the DLK/JNK/SAPK pathway. The abrogation of POS phagocytosis caused a decrease in endomembrane biogenesis and altered endocytosis, exocytosis, transcytosis, and several metabolic and signaling pathways in RCS RPE cells. We also found differential levels of transcripts encoding proteins involved in phagocytosis, vesicle trafficking, the cytoskeleton, retinoic acid, and general metabolism.
- Published
- 2003
28. Gamma-D crystallin gene (CRYGD) mutation causes autosomal dominant congenital cerulean cataracts
- Author
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Ajit K. Basak, Marc Abitbol, Bouchra Benazzouz, Yassir Hajaji, Christine Slingsby, Laurence Arbogast, Latifa Hilal, Olivier Gribouval, A. Berraho, M Cherif-Chefchaouni, S. Boutayeb, Emeline F. Nandrot, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Université Ibn Tofaïl (UIT), Nandrot, Emeline, and Université Ibn Tofail, Faculté des Sciences
- Subjects
Male ,Cerulean ,DNA Mutational Analysis ,Molecular Sequence Data ,Mutation, Missense ,Biology ,bcs ,Cataract ,03 medical and health sciences ,Exon ,0302 clinical medicine ,Crystallin ,Genetics ,medicine ,Coding region ,Humans ,Amino Acid Sequence ,gamma-Crystallins ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Transversion ,Gene ,Genetics (clinical) ,ComputingMilieux_MISCELLANEOUS ,030304 developmental biology ,Genes, Dominant ,Family Health ,0303 health sciences ,Sequence Homology, Amino Acid ,Haplotype ,Chromosome Mapping ,DNA ,medicine.disease ,eye diseases ,Pedigree ,Haplotypes ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Chromosomes, Human, Pair 2 ,Mutation ,030221 ophthalmology & optometry ,Congenital cataracts ,Female ,Original Article ,Lod Score ,Microsatellite Repeats - Abstract
Congenital cataracts are a major cause of bilateral visual impairment in childhood. We mapped the gene responsible for autosomal congenital cerulean cataracts to chromosome 2q33-35 in a four generation family of Moroccan descent. The maximum lod score (7.19 at recombination fraction theta=0) was obtained for marker D2S2208 near the gamma-crystallin gene (CRYG) cluster. Sequencing of the coding regions of the CRYGA, B, C, and D genes showed the presence of a heterozygous CA transversion in exon 2 of CRYGD that is associated with cataracts in this family. This mutation resulted in a proline to threonine substitution at amino acid 23 of the protein in the first of the four Greek key motifs that characterise this protein. We show that although the x ray crystallography modelling does not indicate any change of the backbone conformation, the mutation affects a region of the Greek key motif that is important for determining the topology of this protein fold. Our data suggest strongly that the proline to threonine substitution may alter the protein folding or decrease the thermodynamic stability or solubility of the protein. Furthermore, this is the first report of a mutation in this gene resulting in autosomal dominant congenital cerulean cataracts.
- Published
- 2003
29. Evidence of clinical and genetic heterogeneity in autosomal dominant congenital cerulean cataracts
- Author
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Olivier Gribouval, Emeline F. Nandrot, Bouchra Benazzouz, Marc Abitbol, Latifa Hilal, Jean-Louis Dufier, Yassir Hajaji, M. Belmekki, Mohamed Chefchaouni, Amina Berraho, Siham El Bacha, Université Ibn Tofail, Faculté des Sciences, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Hôpital des Spécialités, Service d’Ophtalmologie B, Rabat, CHU Necker-Enfants Malades, Unité INSERM 423, Université Ibn Tofaïl (UIT), and Nandrot, Emeline
- Subjects
Adult ,Genetic Markers ,Male ,Candidate gene ,Genotype ,Genetic Linkage ,Cerulean ,Chromosomes, Human, Pair 22 ,Chromosome Disorders ,Biology ,Cataract ,genetic heterogeneity ,03 medical and health sciences ,0302 clinical medicine ,Cataracts ,Genetic linkage ,Lens, Crystalline ,beta-Crystallin B Chain ,medicine ,Humans ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Genetics (clinical) ,Genes, Dominant ,030304 developmental biology ,Genetics ,0303 health sciences ,Genetic heterogeneity ,Chromosome ,Middle Aged ,clinical heterogeneity ,medicine.disease ,Congenital cerulean cataract ,Pedigree ,Morocco ,Ophthalmology ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Genetic marker ,Child, Preschool ,Pediatrics, Perinatology and Child Health ,030221 ophthalmology & optometry ,Female ,Lod Score ,Chromosomes, Human, Pair 17 ,Microsatellite Repeats - Abstract
International audience; Autosomal dominant cerulean cataracts (ADCC) have previously been mapped to two loci: one on chromosome 17q24 and the other on chromosome 22q11.2-q12.2, which includes the b-B2 crystallin (CRYBB2) candidate gene. Using polymorphic markers in these regions (D17S802, D17S836, D17S1806 and CRYBB2, D22S258) for linkage analysis, we excluded these loci in a large Moroccan family presenting with an unusual form of ADCC with early onset of lens opacities and rapid evolution. This finding confirms the clinical and genetic heterogeneity of autosomal dominant congenital cerulean cataracts.
- Published
- 2002
30. Visual Impairment, Optical Correction, and Their Impact on Activity Limitations in Elderly Persons: The POLA Study
- Author
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Karine Pérès, Max Villain, Vincent Daien, Isabelle Carrière, Alain Colvez, Cécile Delcourt, Villebrun, Dominique, Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Service d'Ophtalmologie [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Guy de Chauliac, Epidémiologie et Biostatistique [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Caisse Nationale Santé et Solidarité (CNSA), Caisse nationale de solidarité pour l’autonomie (CNSA), Inserm, Fondation de France, Department of Epidemiology of Ageing, Paris, the Fondation pour la Recherche Médicale, Paris, the Région Languedoc-Roussillon, Montpellier, France and the Association Retina-France, Toulouse, Rhônes Poulenc, Essilor, Specia and Horiba ABX Montpellier, Centre de Recherche et d'Information Nutritionnelle, Paris, and Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)
- Subjects
Male ,Activities of daily living ,Visual acuity ,Eye Diseases ,genetic structures ,Vision ,Eye disease ,Optical correction ,Visual Acuity ,MESH: Visual Acuity ,Vision disorder ,Elderly ,MESH: Aged, 80 and over ,0302 clinical medicine ,Surveys and Questionnaires ,030212 general & internal medicine ,MESH: Lenses ,ComputingMilieux_MISCELLANEOUS ,Lenses ,Aged, 80 and over ,MESH: Aged ,MESH: Eye Diseases ,MESH: Middle Aged ,[SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,[SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,MESH: Follow-Up Studies ,Middle Aged ,Refractive Errors ,3. Good health ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,MESH: Vision Disorders ,Female ,Public Health ,medicine.symptom ,Visually Impaired Persons ,medicine.medical_specialty ,Visual impairment ,Vision Disorders ,Vision, Low ,Affect (psychology) ,MESH: Vision, Low ,Article ,03 medical and health sciences ,Physical medicine and rehabilitation ,Internal Medicine ,medicine ,Humans ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Aged ,MESH: Visually Impaired Persons ,MESH: Humans ,business.industry ,MESH: Questionnaires ,Public health ,MESH: Activities of Daily Living ,medicine.disease ,MESH: Male ,eye diseases ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,030221 ophthalmology & optometry ,Optometry ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,MESH: Refractive Errors ,business ,MESH: Female ,MESH: Optometry ,Follow-Up Studies - Abstract
The loss of autonomy among older persons is a major public health issue. In the disablement process model1 chronic and acute conditions lead to psychological and physical deficiencies and ultimately to difficulty performing activities of daily life. In elderly, visual impairment is one of the major deficiencies leading to activity limitations and can be caused by either eye trauma or ocular diseases (affecting the ability to receive or process visual information), or by refractive errors (a failure of the eye to focus images sharply on the retina). Refractive errors affect about a third of the US and Western European populations.2 We estimated the proportion of uncorrected refractive errors and the potential improvement in daily life functioning that could be brought about by optimal visual correction.
- Published
- 2011
31. New VMD2 gene mutations identified in patients affected by Best vitelliform macular dystrophy
- Author
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V Drouin-Garraud, Maurice Menasche, Daniel F. Schorderet, J.L. Dufier, Dominique Bonneau, O Roche, Kuai Yu, Aurore Germain, D Schmidt, Criss Hartzell, Rodolphe Fischmeister, K Bigot, Francis L. Munier, P Le Neindre, Dominique Marchant, Cécile Marsac, Marc Abitbol, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Signalisation et physiopathologie cardiaque, and Université Paris-Sud - Paris 11 (UP11)-IFR141-Institut National de la Santé et de la Recherche Médicale (INSERM)
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Male ,chloride channel ,Patch-Clamp Techniques ,[SDV]Life Sciences [q-bio] ,DNA Mutational Analysis ,Mutant ,Gene mutation ,Kidney ,medicine.disease_cause ,Macular Degeneration ,Exon ,0302 clinical medicine ,Age of Onset ,Bestrophins ,Child ,Genetics (clinical) ,Genes, Dominant ,Genetics ,0303 health sciences ,Mutation ,Exons ,VMD2 (OMIM 153700) ,Transmembrane protein ,Pedigree ,Child, Preschool ,Female ,Recombinant Fusion Proteins ,Best's macular dystrophy ,Mutation, Missense ,Biology ,Transfection ,Cell Line ,Structure-Activity Relationship ,03 medical and health sciences ,Chlorides ,Chloride Channels ,medicine ,Humans ,Point Mutation ,Patch clamp ,Eye Proteins ,030304 developmental biology ,Ion Transport ,Point mutation ,HEK 293 cells ,Sequence Analysis, DNA ,Molecular biology ,Protein Structure, Tertiary ,Amino Acid Substitution ,Mutagenesis, Site-Directed ,030221 ophthalmology & optometry ,Mutant Proteins ,Online Mutation Report ,sense organs - Abstract
Purpose: The mutations responsible for Best Vitelliform Macular Dystrophy (BVMD) are found in a gene called VMD2. The VMD2 gene encodes a transmembrane protein named bestrophin-1 (hBest1) which is a Ca2+-sensitive chloride channel. This study was performed to identify disease-specific mutations in 27 patients with BVMD. Because this disease is characterized by an alteration of the Cl- channel function, patch clamp analysis was used to test the hypothesis that one of the VMD2 mutated variant is indeed causing the disease. Methods: Direct sequencing analysis of the 11 VMD2 exons was performed to detect new abnormal sequences. The mutant of hBest1 was expressed in HEK-293 cells and the associated Cl- current was examined using whole-cell patch clamp. Results: We identified six new VMD2 mutations, located exclusively in exons four, six and eight. One of these mutations (Q293H) is particularly severe. Patch clamp analysis of HEK cells expressing the Q293H mutant shows that this mutant channel is non-functional. Furthermore, the Q293H mutant inhibits the function of wild-type bestrophin-1 channels in a dominant negative manner. Conclusions This study provides further support to the idea that mutations in VMD2 are a necessary factor for Best disease. However, because variable expressivity of VMD2 was observed in family C which carries the Q293H mutation, it is also clear that a disease-linked mutation in VMD2 is not sufficient to produce BVMD. Our finding that the Q293H mutant does not form functional channels in the membrane could be explained either by disruption of channel conductance or gating mechanisms or by improper trafficking of the protein to the plasma membrane.
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- 2006
32. Plasma Lutein and Zeaxanthin and Other Carotenoids as Modifiable Risk Factors for Age-Related Maculopathy and Cataract: The POLA Study
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Wolfgang Schalch, Isabelle Carrière, Pascale Barberger-Gateau, Martine Delage, Cécile Delcourt, Epidémiologie, santé publique et développement, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR99-ISPED, Pathologies du système nerveux : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de biochimie [Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Lapeyronie, Research and Development, DSM Nutritional Products Ltd, Fondation de France, Fondation pour la Recherche Médicale, Région Languedoc-Roussillon, Association Retina-France, Rhônes Poulenc, Essilor, Specia et Centre de Recherche et d'Information Nutritionnelle., POLA Study Group, and Villebrun, Dominique
- Subjects
Male ,Lutein ,genetic structures ,030309 nutrition & dietetics ,Xanthophylls ,MESH: Research Support, Non-U.S. Gov't ,Macular Degeneration ,chemistry.chemical_compound ,0302 clinical medicine ,Risk Factors ,MESH: Risk Factors ,Chromatography, High Pressure Liquid ,0303 health sciences ,education.field_of_study ,MESH: Middle Aged ,[SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,[SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,food and beverages ,Middle Aged ,beta Carotene ,Zeaxanthin ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,MESH: beta Carotene ,Female ,medicine.medical_specialty ,Population ,Drusen ,MESH: Lutein ,Cataract ,03 medical and health sciences ,Zeaxanthins ,Ophthalmology ,medicine ,Humans ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Risk factor ,MESH: Chromatography, High Pressure Liquid ,education ,MESH: Macular Degeneration ,MESH: Humans ,business.industry ,MESH: Xanthophylls ,Macular degeneration ,medicine.disease ,MESH: Male ,eye diseases ,Surgery ,Age-related maculopathy ,chemistry ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,030221 ophthalmology & optometry ,Maculopathy ,MESH: Cataract ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,sense organs ,business ,MESH: Female - Abstract
PURPOSE. To assess the associations of plasma lutein and zeaxanthin and other carotenoids with the risk of age-related maculopathy (ARM) and cataract in the population-based Pathologies Oculaires Liees a l'Age (POLA) Study. METHODS. Retinal photographs were graded according to the international classification. ARM was defined by the presence of late ARM (neovascular ARM, geographic atrophy) and/or soft indistinct drusen (>125 μm) and/or soft distinct drusen (>125 μm) associated with pigmentary abnormalities. Cataract classification was based on a direct standardized lens examination at the slit lamp, according to Lens Opacities Classification System III. Plasma carotenoids were measured by high-performance liquid chromatography (HPLC), in 899 subjects of the cohort. RESULTS. After multivariate adjustment, the highest quintile of plasma zeaxanthin was significantly associated with reduced risk of ARM (OR = 0.07; 95% CI: 0.01-0.58; P for trend = 0.005), nuclear cataract (OR = 0.23; 95% CI: 0.08-0.68; P for trend = 0.003) and any cataract (OR = 0.53; 95% CI: 0.31-0.89; P for trend = 0.01). ARM was significantly associated with combined plasma lutein and zeaxanthin (OR = 0.21; 95% CI: 0.05- 0.79; P for trend = 0.01), and tended to be associated with plasma lutein (OR = 0.31; 95% CI: 0.09-1.07; P for trend = 0.04), whereas cataract showed no such associations. Among other carotenoids, only β-carotene showed a significant negative association with nuclear cataract, but not ARM. CONCLUSIONS. These results are strongly suggestive of a protective role of the xanthophylls, in particular zeaxanthin, for the protection against ARM and cataract.
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- 2006
33. Reduction of brain metastases in plasminogen activator inhibitor-1 deficient mice with transgenic ocular tumors
- Author
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Agnès Noël, Friedrich Beermann, M.M. Petitjean, Paule Opolon, E Frau, Maud Jost, Michel Perricaudet, J.-M. Foidart, Catherine Maillard, Mélanie Mestdagt, Anne Masset, Marc Abitbol, Céline Bouquet, Laboratory of Tumor and Developmental Biology, Université de Liège-CHU Sart-Tilman, Vectorologie et transfert de gènes (VTG / UMR8121), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Centre National de la Recherche Scientifique (CNRS), Swiss Institute for Experimental Cancer Research, ISREC, Centre d'Etudes et de Recherche Thérapeutique en Ophtalmologie (CERTO), Association RETINA France, Partenaires INRAE-Partenaires INRAE, Department of Gynecology and Obstetrics, and CHU Liège
- Subjects
Genetically modified mouse ,Cancer Research ,Pathology ,medicine.medical_specialty ,Angiogenesis ,Transgene ,Blotting, Western ,Mice, Transgenic ,Retinal Pigment Epithelium ,Biology ,Metastasis ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Plasminogen Activator Inhibitor 1 ,medicine ,Animals ,Oligonucleotide Array Sequence Analysis ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,Brain Neoplasms ,Reverse Transcriptase Polymerase Chain Reaction ,Eye Neoplasms ,General Medicine ,medicine.disease ,Primary tumor ,[SDV.BBM.BC]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM] ,chemistry ,030220 oncology & carcinogenesis ,Plasminogen activator inhibitor-1 ,Plasminogen activator ,Brain metastasis - Abstract
Plasminogen activator inhibitor-1 is known to play a paradoxical positive role in tumor angiogenesis, but its contribution to metastatic spread remains unclear. We studied the impact of plasminogen activator inhibitor (PAI)-1 deficiency in a transgenic mouse model of ocular tumors originating from retinal epithelial cells and leading to brain metastasis (TRP-1/SV40 Tag mice). PAI-1 deficiency did not affect primary tumor growth or vascularization, but was associated with a smaller number of brain metastases. Brain metastases were found to be differentially distributed between the two genotypes. PAI-1-deficient mice displayed mostly secondary foci expanding from local optic nerve infiltration, whereas wild-type animals displayed more disseminated nodules in the scissura and meningeal spaces. SuperArray GEarray analyses aimed at detecting molecules potentially compensating for PAI-1 deficiency demonstrated an increase in fibroblast growth factor-1 (FGF-1) gene expression in primary tumors, which was confirmed by reverse transcription-polymerase chain reaction and western blotting. Our data provide the first evidence of a key role for PAI-1 in a spontaneous model of metastasis and suggest that angiogenic factors, such as FGF-1, may be important for primary tumor growth and may compensate for the absence of PAI-1. They identify PAI-1 and FGF-1 as important targets for combined antitumor strategies.
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