90 results on '"Marazova, Katia"'
Search Results
2. Rodent Models of Retinal Degeneration: From Purified Cells in Culture to Living Animals
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Fradot, Valérie, primary, Augustin, Sébastien, additional, Fontaine, Valérie, additional, Marazova, Katia, additional, Guillonneau, Xavier, additional, Sahel, José A., additional, and Picaud, Serge, additional
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- 2023
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3. Gene augmentation in FAM161A ciliopathy: Toward functional vision rescue
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Sahel, José-Alain, primary, Marazova, Katia, additional, and Dalkara, Deniz, additional
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- 2023
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4. Macular Dystrophies: Management and Interventions
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Marazova, Katia, Sahel, José-Alain, Querques, Giuseppe, editor, and Souied, Eric H., editor
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- 2016
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5. Future Therapies for Retinitis Pigmentosa
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Sahel, José-Alain, Marazova, Katia, Puech, Bernard, editor, De Laey, Jean-Jacques, editor, and Holder, Graham E., editor
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- 2014
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6. Vision Restoration by Optogenetic Therapy and Developments Toward Sonogenetic Therapy
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Provansal, Matthieu, Marazova, Katia, Sahel, José Alain, Picaud, Serge, Sahel, José, Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), and Gestionnaire, HAL Sorbonne Université 5
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vision ,restoration ,genetic structures ,Biomedical Engineering ,Vision Disorders ,Visual Acuity ,Review ,optogenetic ,eye diseases ,Optogenetics ,Ophthalmology ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Humans ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Retinitis Pigmentosa ,Vision, Ocular ,sonogenetic - Abstract
International audience; After revolutionizing neuroscience, optogenetic therapy has entered successfully in clinical trials for restoring vision to blind people with degenerative eye diseases, such as retinitis pigmentosa. These clinical trials still have to evaluate the visual acuity achieved by patients and to determine if it reaches its theoretical limit extrapolated from ex vivo experiments. Different strategies are developed in parallel to reduce required light levels and improve information processing by targeting various cell types. For patients with vision loss due to optic atrophy, as in the case of glaucoma, optogenetic cortical stimulation is hampered by light absorption and scattering by the brain tissue. By contrast, ultrasound waves can diffuse widely through the dura mater and the brain tissue as indicated by ultrasound imaging. Based on our recent results in rodents, we propose the sonogenetic therapy relying on activation of the mechanosensitive channel as a very promising vision restoration strategy with a suitable spatiotemporal resolution. Genomic approaches may thus provide efficient brain machine interfaces for sight restoration.
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- 2022
7. Assessing Photoreceptor Status in Retinal Dystrophies: From High-Resolution Imaging to Functional Vision
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Sahel, José-Alain, primary, Grieve, Kate, additional, Pagot, Chloé, additional, Authié, Colas, additional, Mohand-Said, Saddek, additional, Paques, Michel, additional, Audo, Isabelle, additional, Becker, Karine, additional, Chaumet-Riffaud, Anne-Elisabeth, additional, Azoulay, Line, additional, Gutman, Emmanuel, additional, Léveillard, Thierry, additional, Zeitz, Christina, additional, Picaud, Serge, additional, Dalkara, Deniz, additional, and Marazova, Katia, additional
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- 2021
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8. Toward postnatal reversal of ocular congenital malformations
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Sahel, Jose-Alain and Marazova, Katia
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Birth defects -- Health aspects -- Research -- Genetic aspects -- Complications and side effects -- Patient outcomes -- Care and treatment ,Genetic transcription -- Health aspects -- Research ,Health care industry - Abstract
Aniridia is a panocular disorder that severely affects vision in early life. Most cases are caused by dominantly inherited mutations or deletions of the PAX6 gene, which encodes a transcription factor that is essential for the development of the eye and the central nervous system. In this issue of the JCI, Gregory-Evans and colleagues demonstrate that early postnatal topical administration of an ataluren-based formulation reverses congenital malformations in the postnatal mouse eye, providing evidence that manipulation of PAX6 after birth may lead to corrective tissue remodeling. These findings offer hope that ataluren administration could be a therapeutic paradigm applicable to some major congenital eye defects., Mutations that inactivate gene function by promoting premature translational termination cause a large number of human diseases. It is thought that at least one-third of all genetic diseases and many [...]
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- 2014
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9. Functional rescue of cone photoreceptors in retinitis pigmentosa
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Sahel, José-Alain, Léveillard, Thierry, Picaud, Serge, Dalkara, Deniz, Marazova, Katia, Safran, Avinoam, Paques, Michel, Duebel, Jens, Roska, Botond, and Mohand-Said, Saddek
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- 2013
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10. In vitro neuroprotection by novel antioxidants in guinea-pig urinary bladder subjected to anoxia-glucopenia/reperfusion damage
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Pessina, Federica, Marazova, Katia, Ninfali, Paolino, Avanzi, Luca, Manfredini, Stefano, and Sgaragli, Giampietro
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- 2004
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11. Mechanical response to electrical field stimulation of rat, guinea-pig, monkey and human detrusor muscle: a comparative study
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Pessina, Federica, Marazova, Katia, Kalfin, Reni, Sgaragli, Giampietro, Manganelli, Antonio, and Milenov, Kiril
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- 2001
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12. Trypsin is produced by and activates protease-activated receptor-2 in human cancer colon cells: Evidence for new autocrine loop
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Ducroc, Robert, Bontemps, Claire, Marazova, Katia, Devaud, Hélène, Darmoul, Dalila, and Laburthe, Marc
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- 2002
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13. Assessing Photoreceptor Status in Retinal Dystrophies: From High-Resolution Imaging to Functional Vision.
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SAHEL, JOSÉ-ALAIN, GRIEVE, KATE, PAGOT, CHLOÉ, AUTHIÉ, COLAS, MOHAND-SAID, SADDEK, PAQUES, MICHEL, AUDO, ISABELLE, BECKER, KARINE, CHAUMET-RIFFAUD, ANNE-ELISABETH, AZOULAY, LINE, GUTMAN, EMMANUEL, LÉVEILLARD, THIERRY, ZEITZ, CHRISTINA, PICAUD, SERGE, DALKARA, DENIZ, and MARAZOVA, KATIA
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- 2021
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14. Let There Be Light: Gene and Cell Therapy for Blindness
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Dalkara, Deniz, primary, Goureau, Olivier, additional, Marazova, Katia, additional, and Sahel, José-Alain, additional
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- 2016
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15. Optogenetics
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Duebel, Jens, primary, Marazova, Katia, additional, and Sahel, José-Alain, additional
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- 2015
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16. Toward postnatal reversal of ocular congenital malformations
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Sahel, José-Alain, primary and Marazova, Katia, additional
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- 2013
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17. On the mechanisms of the antispasmodic action of some hindered phenols in rat aorta rings
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Fusi, Fabio, primary, Marazova, Katia, additional, Pessina, Federica, additional, Gorelli, Beatrice, additional, Valoti, Massimo, additional, Frosini, Maria, additional, and Sgaragli, Giampietro, additional
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- 2000
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18. Effects of 2,5-di-t-butyl-1,4-benzohydroquinone (BHQ) on rat aorta smooth muscle
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Fusi, Fabio, primary, Gorelli, Beatrice, additional, Valoti, Massimo, additional, Marazova, Katia, additional, and Sgaragli, Gian P, additional
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- 1998
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19. EFFECTS OF CARNITINE AND ITS DERIVATIVES ON GASTRIC ACID SECRETION IN RATS
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VALOTI, MASSIMO, BENOCCI, ALBERTO, MARAZOVA, KATIA, and MANTOVANI, PIERO
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Carnitine is a natural substance that acts as a carrier of fatty-acids across the inner mitochondrial membrane for subsequentβ-oxidation. Acetyl-L-carnitine is the acetyl derivative ofL-carnitine that has been shown to possess a slight cholinomimetic activity. Its success in sports medicine is dependent on the fact that it is able to stimulate the central nervous system functions.This study aims to investigate the effects ofL-carnitine (LC) and its derivatives—acetyl-L-carnitine (ALC) and propionyl-L-carnitine (PLC)—on gastric acid secretion in rats. A concentration-dependent relationship with both ALC or PLC was observed in experimentsin vitrousing a rat isolated stomach. The addition of atropine to the perfusion bath only partially antagonized the effects of the two compounds. Stimulation of gastric acid secretion in a dose-dependent manner was also found when the tested compounds were administered i.v. to anaesthetized rats. To elucidate the mechanism of the gastric secretory response, assay for acetylcholine esterase activity using acetylthiocholine as substrate, was performed. It was found that ALC and PLC inhibited acetylcholine esterase, however, the IC50for both compounds was about four times of magnitude greater than that of eserine.As the increase of the gastric acid secretion promoted by carnitines was blocked only partially by atropine bothin vitroandin vivo, whilst it was completely abolished by experimental degeneration of the sympathetic neurons or by blockade of the postsynaptic sympathetic receptors, it is suggested that the effect of carnitines is determined by cholinergic and partly by adrenergic mechanisms.
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- 1996
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20. Gene-Independent Strategies to Extend Cone Photoreceptors Functional Life
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Sahel, Jose-Alain, Picaud, Serge, Deniz Dalkara, Paques, Michel, Duebel, Jens, Mohand-Said, Saddek, Marazova, Katia, Bertin, Stephane, Ayello-Scheer, Sarah, Jaillard, Celine, Roska, Botond, and Leveillard, Thierry
21. <atl>Trypsin is produced by and activates protease-activated receptor-2 in human cancer colon cells: Evidence for new autocrine loop
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Ducroc, Robert, Bontemps, Claire, Marazova, Katia, Devaud, Hélène, Darmoul, Dalila, and Laburthe, Marc
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COLON cancer , *TRYPSINOGEN - Abstract
In this work, we showed that human colon cancer cell lines produce trypsin which can activate a receptor for trypsin, the protease-activated receptor-2 (PAR-2), in these cells. RT-PCR experiments showed that trypsinogen transcripts were present in four colon cancer cell lines : T84, Caco-2, HT-29 and Cl.19A. By Western blot analysis we found a 25 kDa immunoreactive band identified as trypsinogen I in cell lysates and in the corresponding culture media. Concentrations of trypsin in cell media were found in nanomolar range, thus compatible with activation of protease-activated receptor 2 (PAR-2). This was further demonstrated in a colon cancer cell line (H-29) Ca2+i assay since increases in Ca2+i were observed in response to media from T84, Caco-2 or Cl.19A cells that were similar to that observed with 2–5 nM trypsin and were abolished by trypsin inhibitor. Altogether, these data show that colon cancer cell lines produce and secrete trypsin at concentrations compatible with activation of PAR-2. They support possible autocrine/paracrine regulation of PAR-2 activity by trypsin in colon cancer cells. [Copyright &y& Elsevier]
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- 2002
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22. Assessing Photoreceptor Status in Retinal Dystrophies: From High-Resolution Imaging to Functional Vision
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Michel Paques, Chloé Pagot, Christina Zeitz, José-Alain Sahel, Deniz Dalkara, Isabelle Audo, Serge Picaud, Saddek Mohand-Said, Line Azoulay, Kate Grieve, Katia Marazova, Thierry Leveillard, Karine Becker, Colas N. Authié, Emmanuel Gutman, Anne-Elisabeth Chaumet-Riffaud, Marazova, Katia, University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Sorbonne Université (SU), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Institut de la Vision, 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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medicine.medical_specialty ,Visual acuity ,genetic structures ,[SDV]Life Sciences [q-bio] ,media_common.quotation_subject ,Visual impairment ,Adaptation (eye) ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,03 medical and health sciences ,0302 clinical medicine ,Foveal ,Ophthalmology ,Retinal Dystrophies ,Humans ,AOS Thesis ,Medicine ,Contrast (vision) ,External limiting membrane ,Retrospective Studies ,030304 developmental biology ,media_common ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,0303 health sciences ,business.industry ,eye diseases ,Visual field ,[SDV] Life Sciences [q-bio] ,Cross-Sectional Studies ,medicine.anatomical_structure ,Retinal Cone Photoreceptor Cells ,030221 ophthalmology & optometry ,sense organs ,medicine.symptom ,business ,Tomography, Optical Coherence - Abstract
International audience; Purpose: To describe the value of integrating phenotype/genotype data, disease staging, and evaluation of functional vision in patient-centered management of retinal dystrophies.Methods: (1) Cross-sectional structure-function and retrospective longitudinal studies to assess the correlations between standard fundus autofluorescence (FAF), optical coherence tomography, visual acuity (VA), and perimetry (visual field [VF]) examinations to evaluate photoreceptor functional loss in a cohort of patients with rod-cone dystrophy (RCD); (2) flood-illumination adaptive optics (FIAO) imaging focusing on photoreceptor misalignment and orientation of outer segments; and (3) evaluation of the impact of visual impairment in daily life activities, based on functional (visual and mobility) vision assessment in a naturalistic environment in visually impaired subjects with RCD and subjects treated with LuxturnaⓇ for RPE65-related Leber congenital amaurosis before and after therapy.Results: The results of the cross-sectional transversal study showed that (1) VA and macular sensitivity were weakly correlated with the structural variables; and (2) functional impairment (VF) was correlated with reduction of anatomical markers of photoreceptor structure and increased width of autofluorescent ring. The dimensions of the ring of increased FAF evolved faster. Other criteria that differed among groups were the lengths of the ellipsoid zone, the external limiting membrane, and the foveal thickness. FIAO revealed a variety of phenotypes: paradoxical visibility of foveal cones; heterogeneous brightness of cones; dim, inner segment-like, and RPE-like mosaic. Directional illumination by varying orientation of incident light (Stiles-Crawford effect) and the amount of side illumination (gaze-dependent imaging) affected photoreceptor visibility. Mobility assessment under different lighting conditions showed correlation with VF, VA, contrast sensitivity (CS), and dark adaptation, with different predictive values depending on mobility study paradigms and illumination level. At high illumination level (235 lux), VF was a predictor for all mobility performance models. Under low illumination (1 and 2 lux), VF was the most significant predictor of mobility performance variables, while CS best explained the number of collisions and segments. In subjects treated with LuxturnaⓇ, a very favorable impact on travel speed and reduction in the number of collisions, especially at low luminance, was observable 6 months following injection, in both children and adults.Conclusions: Our results suggest the benefit of development and implementation of quantitative and reproducible tools to evaluate the status of photoreceptors and the impact of both visual impairment and novel therapies in real-life conditions. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
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- 2021
23. Single and Multisite Graphene-Based Electroretinography Recording Electrodes: A Benchmarking Study
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Jose de la Cruz, Diep Nguyen, Xavi Illa, Jessica Bousquet, Antonio P. Pérez‐Marín, Elena del Corro, Serge Picaud, Jose A. Garrido, Clement Hebert, European Commission, Ministerio de Ciencia, Innovación y Universidades (España), Agencia Estatal de Investigación (España), Agence Nationale de la Recherche (France), Generalitat de Catalunya, Ministerio de Economía y Competitividad (España), Catalan Institute of Nanoscience and Nanotechnology (ICN2), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Barcelona Institute of Science and Technology (BIST), Barcelona Institute of Science and Technology (BIST), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Instituto de Microelectrònica de Barcelona (IMB-CNM), Centro Nacional de Microelectronica [Spain] (CNM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), and Marazova, Katia
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[SDV] Life Sciences [q-bio] ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MEA ,Mechanics of Materials ,ERG ,[SDV]Life Sciences [q-bio] ,graphene ,General Materials Science ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Industrial and Manufacturing Engineering ,photoreceptor degeneration - Abstract
Electroretinography (ERG) is a clinical test employed to understand and diagnose many retinopathies. ERG is usually performed by placing a macroscopic ring gold wire electrode on the cornea while flashing light onto the eye to measure changes in the transretinal potential. However, macroscopic gold electrodes are severely limiting since they do not provide a flexible interface to contact the sensitive corneal tissue, making this technique highly uncomfortable for the patient. Another major drawback is the opacity of gold electrodes, which only allows them to record the ERG signal on the corneal periphery, preventing central ERG recordings. To overcome the limitations of metal-based macroscopic ERG electrodes, flexible electrodes are fabricated using graphene as a transparent, flexible, and sensitive material. The transparency of the graphene is exploited to fabricate microelectrode arrays (MEAs) that are able to perform multisite recording on the cornea. The graphene-based ERG electrodes are benchmarked against the widely used gold electrodes in a P23H rat model with photoreceptor degeneration. This study shows that the graphene-based ERG electrodes can faithfully record ERGs under a wide range of conditions (light intensity, stage of photoreceptor degeneration, etc.) while offering additional benefits for ERG recordings such as transparency and flexibility., J.d.l.C. and D.N. contributed equally to this work. This project received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement nos. 881603 (GrapheneCore3). This work was within the project FIS2017-85787-R funded by the “Ministerio de Ciencia, Innovación y Universidades” of Spain, the “Agencia Estatal de Investigación (AEI),” and the “Fondo Europeo de Desarrollo Regional (FEDER/UE).” Support was also provided by the French state funds managed by the Agence Nationale de la Recherche within the Programme Investissements d'Avenir, LABEX LIFESENSES (ANR-10-LABX-65) and IHU FOReSIGHT (ANR-18-IAHU-0001). The ICN2 is supported by the Severo Ochoa Centres of Excellence program, funded by the Spanish Research Agency (AEI, grant no. SEV-2017-0706), and by the CERCAProgram/Generalitat de Catalunya. E.d.C. acknowledges the Spanish MINECO Juan de la Cierva Fellowship JC-2015-25201. This work made use of the Spanish ICTS Network MICRONANOFABS partially supported by MICINN and the ICTS “NANBIOSIS,” more specifically by the Micro-NanoTechnology Unit of the CIBER in Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN) at the IMB-CNM. J.d.l.C. would like to thank Laura García for the work on the images and figures throughout the whole paper writing process. E.d.C acknowledges the grant RYC2019-027879-I financed by MCIN/AEI /10.13039/501100011033. The project leading to these results have received funding from “la Caixa” Foundation (ID 100010434), under the agreement LCF/PR/HR19/52160003. These activities are co-funded with 50% by the European Regional Development Fund under the framework of the ERFD Operative Programme for Catalunya 2014–2020 with the support of the Department de Recerca i Universitat (GraphCAT 001-P-001702).
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- 2022
24. First Evidence of Natural SARS-CoV-2 Infection in Domestic Rabbits
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Fritz, Matthieu, de Riols de Fonclare, Daphné, Garcia, Déborah, Beurlet, Stéphanie, Becquart, Pierre, Rosolen, Serge, Briend-Marchal, Alexandra, Leroy, Eric, Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Vebiotel - Laboratoire de Biologie Vétérinaire, Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Marazova, Katia, and ANR-20-CO11-0002,CoVet,Etude sérologique géographique et temporelle à grande échelle de l'infection des animaux de compagnie par le SARS-CoV-2 au cours de la deuxième vague épidémique de COVID-19 en France(2020)
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rabbits ,[SDV.BA.MVSA]Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,SARS-CoV-2 ,microsphere immunoassay ,viruses ,[SDV.BA.MVSA] Life Sciences [q-bio]/Animal biology/Veterinary medicine and animal Health ,virus diseases ,COVID-19 ,serology ,one health ,[SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie ,Luminex ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,France ,pet rabbit - Abstract
International audience; We tested 144 pet rabbits sampled in France between November 2020 and June 2021 for antibodies to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by microsphere immunoassay. We reported the first evidence of a natural SARS-CoV-2 infection in rabbits with a low observed seroprevalence between 0.7% and 1.4%
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- 2022
25. Nonretinoid chaperones improve rhodopsin homeostasis in a mouse model of retinitis pigmentosa
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Abhishek Vats, Yibo Xi, Bing Feng, Owen D. Clinger, Anthony J. St. Leger, Xujie Liu, Archisha Ghosh, Chase D. Dermond, Kira L. Lathrop, Gregory P. Tochtrop, Serge Picaud, Yuanyuan Chen, McGowan Institute for Regenerative Medicine [Pittsburgh, PA, USA] (MGIRM), University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Pennsylvania Commonwealth System of Higher Education (PCSHE), Case Western Reserve University [Cleveland], Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), and Marazova, Katia
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Pharmacology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Rhodopsin ,[SDV]Life Sciences [q-bio] ,G protein–coupled receptors ,General Medicine ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,[SDV] Life Sciences [q-bio] ,Ophthalmology ,Disease Models, Animal ,Mice ,Retinal Rod Photoreceptor Cells ,NIH 3T3 Cells ,Animals ,Homeostasis ,Retinitis Pigmentosa ,Neuroscience ,Protein misfolding ,Molecular Chaperones - Abstract
International audience; Rhodopsin-associated (RHO-associated) retinitis pigmentosa (RP) is a progressive retinal disease that currently has no cure. RHO protein misfolding leads to disturbed proteostasis and the death of rod photoreceptors, resulting in decreased vision. We previously identified nonretinoid chaperones of RHO, including YC-001 and F5257-0462, by small-molecule high-throughput screening. Here, we profile the chaperone activities of these molecules toward the cell-surface level of 27 RP-causing human RHO mutants in NIH3T3 cells. Furthermore, using retinal explant culture, we show that YC-001 improves retinal proteostasis by supporting RHO homeostasis in RhoP23H/+ mouse retinae, which results in thicker outer nuclear layers (ONL), indicating delayed photoreceptor degeneration. Interestingly, YC-001 ameliorated retinal immune responses and reduced the number of microglia/macrophages in the RhoP23H/+ retinal explants. Similarly, F5257-0462 also protects photoreceptors in RhoP23H/+ retinal explants. In vivo, intravitreal injection of YC-001 or F5257-0462 microparticles in PBS shows that F5257-0462 has a higher efficacy in preserving photoreceptor function and delaying photoreceptor death in RhoP23H/+ mice. Collectively, we provide proof of principle that nonretinoid chaperones are promising drug candidates in treating RHO-associated RP.
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- 2021
26. Functional ultrasound imaging of deep visual cortex in awake nonhuman primates
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Pierre Pouget, José-Alain Sahel, Mathias Fink, Harry Ahnine, Frédéric Chavane, Fabrice Arcizet, Mickael Tanter, Kevin Blaize, Serge Picaud, Ulisse Ferrari, Marc Gesnik, Thomas Deffieux, Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Physique pour la médecine (PhysMed Paris), Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau = Paris Brain Institute (ICM), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut de Neurosciences de la Timone (INT), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Institut Langevin - Ondes et Images (UMR7587) (IL), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), ANR-10-LABX-0065,LIFESENSES,DES SENS POUR TOUTE LA VIE(2010), ANR-18-IAHU-0001,FOReSIGHT,Enabling Vision Restoration(2018), European Project: 610110,EC:FP7:ERC,ERC-2013-SyG,HELMHOLTZ(2014), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de recherche cerveau et cognition (CERCO), Institut des sciences du cerveau de Toulouse. (ISCT), Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre National de la Recherche Scientifique (CNRS), Sorbonne Université (SU)-Ecole Superieure de Physique et de Chimie Industrielles de la Ville de Paris (ESPCI Paris), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université de Paris (UP)-Centre National de la Recherche Scientifique (CNRS), Institut du Cerveau et de la Moëlle Epinière = Brain and Spine Institute (ICM), Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Université Paris sciences et lettres (PSL), Aix Marseille Université (AMU), Marazova, Katia, and Pouget, Pierre
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Male ,Brain activity and meditation ,Computer science ,[SDV]Life Sciences [q-bio] ,brain imaging ,nonhuman primate ,functional ultrasound imaging ,ocular dominance ,Ocular dominance ,03 medical and health sciences ,[SPI]Engineering Sciences [physics] ,Spatio-Temporal Analysis ,Engineering ,0302 clinical medicine ,Neuroimaging ,medicine ,Animals ,Wakefulness ,visual cortex ,Ultrasonography ,030304 developmental biology ,Brain Mapping ,0303 health sciences ,Multidisciplinary ,[SCCO.NEUR]Cognitive science/Neuroscience ,[SCCO.NEUR] Cognitive science/Neuroscience ,Reproducibility of Results ,Biological Sciences ,Macaca mulatta ,[SDV] Life Sciences [q-bio] ,Dominance, Ocular ,Visual cortex ,medicine.anatomical_structure ,Physical Sciences ,Fixation (visual) ,Imaging technology ,Ultrasound imaging ,Female ,Spatiotemporal resolution ,Neuroscience ,Photic Stimulation ,030217 neurology & neurosurgery - Abstract
Significance Nowadays, several techniques exist to study and better understand how the brain works (fMRI, EEG, electrophysiology, etc.). Each has its own advantages and disadvantages (spatiotemporal resolution, maximal recording depth, signal-to-noise ratio, etc.). In this article, we show that the new functional ultrasound (fUS) imaging technique is appropriate to record and map brain activity in awake primates on a scale previously unreachable. It allows distinguishing patterns similar to ocular dominance bands in the visual cortex through all layers of the cortex, which was impossible before with common techniques. This paper demonstrates the utility of fUS imaging for studying brain activity in awake primates and its interest to all neuroscientists., Deep regions of the brain are not easily accessible to investigation at the mesoscale level in awake animals or humans. We have recently developed a functional ultrasound (fUS) technique that enables imaging hemodynamic responses to visual tasks. Using fUS imaging on two awake nonhuman primates performing a passive fixation task, we constructed retinotopic maps at depth in the visual cortex (V1, V2, and V3) in the calcarine and lunate sulci. The maps could be acquired in a single-hour session with relatively few presentations of the stimuli. The spatial resolution of the technology is illustrated by mapping patterns similar to ocular dominance (OD) columns within superficial and deep layers of the primary visual cortex. These acquisitions using fUS suggested that OD selectivity is mostly present in layer IV but with extensions into layers II/III and V. This imaging technology provides a new mesoscale approach to the mapping of brain activity at high spatiotemporal resolution in awake subjects within the whole depth of the cortex.
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- 2020
27. Gene augmentation in FAM161A ciliopathy: Toward functional vision rescue
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Sahel, José-Alain, Marazova, Katia, and Dalkara, Deniz
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28. Inherited Retinal Degenerations: Current Landscape and Knowledge Gaps
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Jacque L. Duncan, Amy M. Laster, John D. Ash, Stephen P. Daiger, John G. Flannery, Alessandro Iannaccone, Eric A. Pierce, Marco A. Zarbin, Jose A. Sahel, David G. Birch, Donald J. Zack, University of California [San Francisco] (UC San Francisco), University of California (UC), Harvard Medical School [Boston] (HMS), Foundation Fighting Blindness [Columbia, MD, USA] (2FB), University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Retina Foundation of the Southwest [allas, TX, USA] (RFS), University of Florida [Gainesville] (UF), Duke University School of Medicine [Durham, NC, USA], University of California [Berkeley] (UC Berkeley), Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), Johns Hopkins University School of Medicine [Baltimore], Rutgers University [Newark], Rutgers University System (Rutgers), Foundation Fighting Blindness Scientific Advisory Board, and Marazova, Katia
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0301 basic medicine ,Retinal degeneration ,genetic structures ,Genetic enhancement ,[SDV]Life Sciences [q-bio] ,Biomedical Engineering ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,and the Foundation Fighting Blindness Scientific Advisory Board ,Bioinformatics ,03 medical and health sciences ,chemistry.chemical_compound ,Opthalmology and Optometry ,medicine ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,business.industry ,Genetic heterogeneity ,Mechanism (biology) ,Retinal ,Macular degeneration ,medicine.disease ,eye diseases ,[SDV] Life Sciences [q-bio] ,Ophthalmology ,030104 developmental biology ,RPE65 ,chemistry ,Perspective ,Identification (biology) ,business - Abstract
Inherited retinal degenerations (IRDs) represent a diverse group of progressive, visually debilitating diseases that can lead to blindness in which mutations in genes that are critical to retinal function lead to progressive photoreceptor cell death and associated vision loss. IRDs are genetically heterogeneous, with over 260 disease genes identified to date.1 The development of treatments and cures to modify the rate of disease progression has been limited to date, with some success of neurotrophic factor therapy and gene therapies reported from clinical trials.2–11 The best example of treatment success is gene augmentation therapy for IRD caused by mutations in the RPE65 gene, which recently received US Food and Drug Administration (FDA) approval, which in fact represented the first FDA-approved gene therapy (GT) for any genetically inherited disease.4–9 Recent developments in the IRD field have advanced understanding of the mechanisms responsible for vision loss, creating new opportunities to intervene in the course of disease by developing new therapeutic approaches. In 2013, a Delphi-style gathering of IRD experts led to the identification, by consensus, of top priorities to advance therapeutic efforts for IRDs, including the need for systematic genotyping, improved standardization of visual function testing, development of more rigorous and widespread data collection protocols, and increased data sharing.12 This document summarizes more recent advances in the IRD field and outlines specific knowledge gaps. These knowledge gaps present opportunities for further investigation to enable development of therapies that may slow down or prevent vision loss, or restore vision, in affected patients. Atrophic age-related macular degeneration (AMD) is included among the target inherited retinal diseases of interest because first, understanding AMD may contribute to understanding of inherited macular diseases, and second, understanding of the genetics and mechanism of inherited macular degenerations may contribute to understanding of AMD.
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- 2018
29. Safety of rAAV2/2-ND4 Gene Therapy for Leber Hereditary Optic Neuropathy
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Nitza Thomasson, Serge Fitoussi, Sandrine Meunier, Jean-François Girmens, Barrett Katz, Bernard Gilly, Anne Galy, José-Alain Sahel, Samuel Bidot, Jean Philippe Combal, Sonia Valero, Laure Blouin, Céline Bouquet, Scott Uretsky, Catherine Vignal, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre d'investigation clinique Quinze-Vingts [CHNO] (CIC1423 - CIC QUINZE-VINGTS), Institut Hospitalo-Universitaire FOReSIGHT, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO)-Sorbonne Université (SU), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), GenSight Biologics, Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), University of Pittsburgh School of Medicine, Pennsylvania Commonwealth System of Higher Education (PCSHE), University of Pittsburgh Medical Center [Pittsburgh, PA, États-Unis] (UPMC), and Marazova, Katia
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Male ,LEBER HEREDITARY OPTIC NEUROPATHY ,Genetic enhancement ,[SDV]Life Sciences [q-bio] ,Genetic Vectors ,Visual Acuity ,Visual Physiology ,MEDLINE ,Optic Atrophy, Hereditary, Leber ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Bioinformatics ,Contrast Sensitivity ,03 medical and health sciences ,0302 clinical medicine ,Electroretinography ,medicine ,Humans ,Prospective Studies ,Prospective cohort study ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Color Vision ,medicine.diagnostic_test ,business.industry ,NADH Dehydrogenase ,Genetic Therapy ,Dependovirus ,Middle Aged ,Clinical trial ,[SDV] Life Sciences [q-bio] ,Ophthalmology ,Intravitreal Injections ,030221 ophthalmology & optometry ,Evoked Potentials, Visual ,Female ,business ,030217 neurology & neurosurgery - Abstract
International audience; No abstract available
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- 2018
30. Let there be light: gene and cell therapy for blindness
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José-Alain Sahel, Deniz Dalkara, Olivier Goureau, Katia Marazova, Marazova, Katia, Sorbonne Universités à Paris pour l'Enseignement et la Recherche - - SUPER2011 - ANR-11-IDEX-0004 - IDEX - VALID, 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), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Département Ophtalomologie Pathologies Vitréo-Rétiniennes, Fondation Ophtalmologique Adolphe de Rothschild, This work was supported by the Institut National de la Santé et de la Recherche Médicale (INSERM), Pierre et Marie Curie University (UPMC), the Centre National de la Recherche Scientifique (CNRS), Foundation Fighting Blindness (FFB) [CD-CL-0808-0466-CHNO], ANR-11-IDEX-0004,SUPER,Sorbonne Universités à Paris pour l'Enseignement et la Recherche(2011), 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 Fondation Ophtalmologique Adolphe de Rothschild [Paris]
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0301 basic medicine ,Retinal degeneration ,cis-trans-Isomerases ,genetic structures ,Degenerative Disorder ,Genetic enhancement ,[SDV]Life Sciences [q-bio] ,Genetic Vectors ,Leber Congenital Amaurosis ,Cell- and Tissue-Based Therapy ,Reviews ,Stem cells ,Bioinformatics ,Blindness ,Retina ,AAV vectors ,03 medical and health sciences ,Macular Degeneration ,Degenerative disease ,Retinitis pigmentosa ,Genetics ,medicine ,Humans ,Stargardt Disease ,Molecular Biology ,Clinical Trials as Topic ,business.industry ,Adenoviruses, Human ,Lentivirus ,Genetic Therapy ,Gene Therapy ,Macular degeneration ,Dependovirus ,medicine.disease ,eye diseases ,3. Good health ,Stargardt disease ,Optogenetics ,[SDV] Life Sciences [q-bio] ,030104 developmental biology ,Cis-trans-Isomerases ,Molecular Medicine ,CRISPR-Cas Systems ,business ,Retinitis Pigmentosa - Abstract
International audience; Retinal degenerative diseases are a leading cause of irreversible blindness. Retinal cell death is the main cause of vision loss in genetic disorders such as retinitis pigmentosa, Stargardt disease and Leber congenital amaurosis, as well as in complex age-related diseases such as age-related macular degeneration (AMD). For these blinding conditions, gene and cell therapy approaches offer therapeutic intervention at various disease stages. The present review outlines recent advances in therapies for retinal degenerative disease, focusing on the progress and challenges in the development and clinical translation of gene and cell therapies. A significant body of preclinical evidence and initial clinical results pave the way for further development of these cutting edge treatments for patients with retinal degenerative disorders.
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- 2016
31. Nxnl2 splicing results in dual functions in neuronal cell survival and maintenance of cell integrity
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Aurélie Mouret, Therese Cronin, Thierry Leveillard, José-Alain Sahel, Bernd Kinzel, Marie-Laure Niepon, Olivier Poch, Najate Aït-Ali, Céline Jaillard, Ying Yang, Géraldine Millet-Puel, Alain Trembleau, Wolfgang Raffelsberger, Tina Sedmak, Jean Bennett, Pierre-Marie Lledo, Emmanuelle Clérin, Uwe Wolfrum, Irene Lee-Rivera, 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), Perception et Mémoire, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Johannes Gutenberg - Universität Mainz (JGU), 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), Novartis Pharma AG, Neurobiologie des processus adaptatifs (NPA), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Scheie Eye Institute, University of Pennsylvania [Philadelphia], This work was supported by Inserm, ANR-Neuro 2005 and ANR-MNP 2008 Grants., Marazova, Katia, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), and University of Pennsylvania
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Sensory Receptor Cells ,genetic structures ,Cell Survival ,RNA Splicing ,Sensory system ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Olfaction ,Biology ,Article ,Mice ,03 medical and health sciences ,Thioredoxins ,0302 clinical medicine ,Retinal Rod Photoreceptor Cells ,Genetics ,Animals ,Eye Proteins ,Molecular Biology ,Gene ,Cells, Cultured ,Genetics (clinical) ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,0303 health sciences ,General Medicine ,Anatomy ,Cell biology ,RNA splicing ,Thioredoxin ,030217 neurology & neurosurgery ,Function (biology) - Abstract
International audience; The rod-derived cone viability factors, RdCVF and RdCVF2, have potential therapeutical interests for the treatment of inherited photoreceptor degenerations. In the mouse lacking Nxnl2, the gene encoding RdCVF2, the progressive decline of the visual performance of the cones in parallel with their degeneration, arises due to the loss of trophic support from RdCVF2. In contrary, the progressive loss of rod visual function of the Nxnl2-/- mouse results from a decrease in outer segment length, mediated by a cell autonomous mechanism involving the putative thioredoxin protein RdCVF2L, the second spliced product of the Nxnl2 gene. This novel signaling mechanism extends to olfaction as shown by the progressive impairment of olfaction in aged Nxnl2-/- mice and the protection of olfactory neurons by RdCVF2. This study shows that Nxnl2 is a bi-functional gene involved in the maintenance of both the function and the viability of sensory neurons.
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- 2012
32. Poppers-Associated Retinal Toxicity
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Michel Paques, José-Alain Sahel, Isabelle Audo, Catherine Vignal-Clermont, Fondation Ophtalmologique Adolphe de Rothschild, 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), Supported by Foundation Fighting Blindness (FFB Grant CD-CL-0808-0466-CHNO, FFB Grant C-CMM-0907-0428-INSERM04 for IA)., Fondation Ophtalmologique Adolphe de Rothschild [Paris], 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 Marazova, Katia
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[SDV.GEN]Life Sciences [q-bio]/Genetics ,Pathology ,medicine.medical_specialty ,Recreational Drug ,business.industry ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,General Medicine ,Pharmacology ,humanities ,3. Good health ,Nitric oxide ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Retinal toxicity ,chemistry ,Toxicity ,030221 ophthalmology & optometry ,Medicine ,Nitrite ,business ,ComputingMilieux_MISCELLANEOUS ,030217 neurology & neurosurgery - Abstract
To the Editor: “Poppers” (slang for various forms of alkyl nitrite) are volatile nitric oxide donors that have been used for decades as recreational drugs. Both the popularity of and legal toleranc...
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- 2010
33. CRB1 mutations in inherited retinal dystrophies
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Thierry Léveillard, Aline Antonio, Christine Lonjou, Saddek Mohand-Said, Wassila Carpentier, Shomi S. Bhattacharya, Aurore Germain, Kinga M. Bujakowska, Jean-Paul Saraiva, José-Alain Sahel, Isabelle Audo, Marie-Elise Lancelot, Mélanie Letexier, Christina Zeitz, Marazova, Katia, 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), UCL-Institute of Ophthalmology, IntegraGen SA, Plateforme Post-génomique de la Pitié-Salpêtrière (P3S), UMS omique (OMIQUE), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation Ophtalmologique Adolphe de Rothschild, Department of Celular Therapy and Regenerative Medicine (CABIMER), Andalusian Molecular Biology and Regenerative Medicine Centre, Foundation Fighting Blindness (I.A. FFB Grant No: CD-CL-0808- 0466-CHNO and the CIC503 recognized as an FFB center, FFB Grant No: C-CMM- inserm-00640122, version 1 - 10 Nov 2011 0907-0428-INSERM04), Agence Nationale de la Recherche (SSB), Fondation Voir et Entendre (CZ), GIS-maladies rares (CZ), Ville de Paris and Région Ile de France, National Institutes of Health (USA) (KB NIH, Grant No: 1R01EY020902 - 01A1)., European Commission, Foundation Fighting Blindness, Agence Nationale de la Recherche (France), Fondation Voir et Entendre, Région Ile-de-France, National Institutes of Health (US), 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), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC), and Fondation Ophtalmologique Adolphe de Rothschild [Paris]
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genetic structures ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,MESH: Retinal Dystrophies ,medicine.disease_cause ,MESH: Genotype ,0302 clinical medicine ,MESH: Eye Proteins ,Prevalence ,MESH: Nerve Tissue Proteins ,Rod-cone dystrophy ,Genetics (clinical) ,MESH: Genetic Association Studies ,Genetics ,0303 health sciences ,Mutation ,CRB1 ,LCA ,3. Good health ,Retinitis pigmentosa ,Retinal telangiectasia ,medicine.anatomical_structure ,Phenotype ,rod-cone dystrophy ,MESH: Membrane Proteins ,Retinal Dystrophies ,Retinitis Pigmentosa ,RP ,MESH: Mutation ,Genotype ,Nerve Tissue Proteins ,Biology ,MESH: Phenotype ,Article ,03 medical and health sciences ,medicine ,Humans ,Eye Proteins ,Genetic Association Studies ,MESH: Prevalence ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Retinal pigment epithelium ,MESH: Humans ,Genetic heterogeneity ,Membrane Proteins ,medicine.disease ,030221 ophthalmology & optometry ,sense organs - Abstract
PMCID: PMC3293109.-- et. al., Mutations in the CRB1 gene are associated with variable phenotypes of severe retinal dystrophies, ranging from leber congenital amaurosis (LCA) to rod–cone dystrophy, also called retinitis pigmentosa (RP). Moreover, retinal dystrophies resulting from CRB1 mutations may be accompanied by specific fundus features: preservation of the para-arteriolar retinal pigment epithelium (PPRPE) and retinal telangiectasia with exudation (also referred to as Coats-like vasculopathy). In this publication, we report seven novel mutations and classify over 150 reported CRB1 sequence variants that were found in more that 240 patients. The data from previous reports were used to analyze a potential correlation between CRB1 variants and the clinical features of respective patients. This meta-analysis suggests that the differential phenotype of patients with CRB1 mutations is due to additional modifying factors rather than particular mutant allele combination. Hum Mutat 33:306–315, 2012. © 2011 Wiley Periodicals, Inc., The project was financially supported by the Foundation Fighting Blindness (I.A. FFB Grant No: CD-CL-0808-0466-CHNO and the CIC503 recognized as an FFB center, FFB Grant No: C-CMM-0907-0428-INSERM04), Agence Nationale de la Recherche (SSB), Fondation Voir et Entendre (CZ), GIS-maladies rares (CZ), Ville de Paris and Région Ile de France, National Institutes of Health (USA) (KB NIH, Grant No: 1R01EY020902 - 01A1). European Reintegration Grant PERG04-GA-2008-231125 (to K.B.).
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- 2012
34. RP1 and autosomal dominant rod-cone dystrophy: novel mutations, a review of published variants, and genotype-phenotype correlation.: RP1mutations in French adRP patients
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Audo, Isabelle, Mohand-Saïd, Saddek, Dhaenens, Claire-Marie, Germain, Aurore, Orhan, Elise, Antonio, Aline, Hamel, Christian, Sahel, José-Alain, Bhattacharya, Shomi, Zeitz, Christina, 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), UCL-Institute of Ophthalmology, UF Génopathies - Laboratoire de Biochimie et Biologie Moléculaire [Lille] (LBBM), Université de Lille, Sciences et Technologies-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre de référence des affections sensorielles d'origine génétique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui De Chaulliac, Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), Fondation Ophtalmologique Adolphe de Rothschild, Department of Celular Therapy and Regenerative Medicine (CABIMER), Andalusian Molecular Biology and Regenerative Medicine Centre, The project was financially supported by the Department of Paris, Foundation Fighting Blindness (I.A. FFB Grant N°: CD-CL-0808-0466-CHNO and the CIC503 recognized as an FFB center, FFB Grant No: C-CMM-0907-0428-INSERM04), ANR (S.S.B). NIHR Biomedical Research Centre for Ophthalmology and The Special Trustees of Moorfields Eye Hospital London, Foundation Voir et Entendre (C.Z) and French Ministry of Health (C.H. PHRC # 2008-A01238-47)., and Marazova, Katia
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[SDV.GEN]Life Sciences [q-bio]/Genetics ,sense organs ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,eye diseases - Abstract
International audience; Rod-cone dystrophies (RP) are a clinically and genetically heterogeneous group of inherited retinal disorders characterized by photoreceptor degeneration. RP1 is a major gene underlying autosomal dominant (ad) RP though prevalence figures vary depending on the origin of the cases from 0%-10% of all adRP. Some mutations in RP1 also lead to autosomal recessive RP. Herein we review all previously reported and several novel RP1 mutations in relation to the associated phenotype in patients from a French adRP cohort. Prevalence studies from this cohort show that 5.3% of the cases have RP1 mutations. This is in accordance with other studies reported from UK and USA. The majority of mutations represent truncating mutations which are located in a hot spot region of the gene. Similarly, we identified in total four novel deletions and nonsense mutations, of which two may represent recurrent mutations in this population. In addition a novel missense mutation of uncertain pathogenicity was identified. Including our findings, to date 43 RP1 mutations are known to cause adRP. Variable penetrance of the disease was observed in our and other cohorts. Most patients with RP1 mutations show classical signs of RP with relatively preserved central vision and visual field. ©2011 Wiley Periodicals, Inc.
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- 2012
35. Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death
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José-Alain Sahel, Alain Gaudric, David Mercier, David G. Charteris, Raymond Ripp, Wolfgang Raffelsberger, Ramin Tadayoni, Jean-Denis Muller, F. Metge, Thierry Léveillard, Marie-Noëlle Delyfer, Georges Caputo, Jean-François Korobelnik, Olivier Poch, P.O. Barale, Institut de la Vision, Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Equipe 14 - Inflammation dans la dégénérescence neuronale et le remodelage vasculaire (Inserm U968/CNRS UMR7210/UPMC UM80), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-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), Unité Rétine, Uvéite et Neuro-Ophtalmologie, CHU Bordeaux [Bordeaux], 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), Laboratoire Information, Modèles, Apprentissage [Gif-sur-Yvette] (LIMA), Département Métrologie Instrumentation & Information (DM2I), Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay, 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), Département Ophtalmologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Vitreo-retinal Unit, Moorfields Eye Hospital, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), 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), The work was supported by the Institut National de la Santé et de la Recherche Médicale, CNRS, University of Strasbourg and the network Réseaux National de Génopôles (RNG 209)., Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Fondation Ophtalmologique Adolphe de Rothschild, Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Direction de Recherche Technologique (CEA) (DRT (CEA)), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Laboratoire d'Intégration des Systèmes et des Technologies (LIST), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière, Centre Ophtalmologique des Quinze-Vingts, 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 Marazova, Katia
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Retinal degeneration ,Pathology ,Microarrays ,Visual System ,Gene regulatory network ,degeneration ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,SLCO4A1 ,immune response ,Transcriptome ,Mice ,chemistry.chemical_compound ,Molecular cell biology ,0302 clinical medicine ,[STAT.AP] Statistics [stat]/Applications [stat.AP] ,retinal surgery ,Neurobiology of Disease and Regeneration ,Gene Regulatory Networks ,histocompatibility ,Mathematical Computing ,0303 health sciences ,[STAT.AP]Statistics [stat]/Applications [stat.AP] ,Multidisciplinary ,[STAT.ME] Statistics [stat]/Methodology [stat.ME] ,Cell Death ,Reverse Transcriptase Polymerase Chain Reaction ,Statistics ,Retinal Degeneration ,Neurodegeneration ,neurodegeneration ,Retinal detachment ,Genomics ,Middle Aged ,Sensory Systems ,3. Good health ,medicine.anatomical_structure ,[SDV.MHEP.OS] Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,Medicine ,Retinal Disorders ,medicine.symptom ,Information Technology ,[STAT.ME]Statistics [stat]/Methodology [stat.ME] ,Research Article ,Photoreceptor Cells, Vertebrate ,Adult ,medicine.medical_specialty ,Science ,DNA transcription ,Down-Regulation ,Inflammation ,Biology ,PKD2L1 ,transcriptome of human retinal tissues ,pharmacological target ,Databases ,Young Adult ,03 medical and health sciences ,Genomic Medicine ,statistical analysis ,medicine ,Animals ,Humans ,[SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs ,therapeutic strategy ,Aged ,030304 developmental biology ,Clinical Genetics ,Retina ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,gene HLA-C ,death of photoreceptor cells ,photoreceptor damage ,Immunity ,Computational Biology ,Reproducibility of Results ,Retinal ,medicine.disease ,Computing Methods ,Ophthalmology ,Kinetics ,chemistry ,inflammation ,Computer Science ,030221 ophthalmology & optometry ,Clinical Immunology ,Gene expression ,Genome Expression Analysis ,Pharmacogenomics ,Neuroscience ,Mathematics ,Biomarkers - Abstract
International audience; BACKGROUND: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome. METHODOLOGY/PRINCIPAL FINDINGS: Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here. CONCLUSIONS/SIGNIFICANCE: This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.
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- 2011
36. Quality versus quantity: assessing individual research performance
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José-Alain Sahel, Marazova, Katia, 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), Fondation Ophtalmologique Adolphe de Rothschild, Institute of Ophthalmology, University College of London [London] (UCL), 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 Fondation Ophtalmologique Adolphe de Rothschild [Paris]
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Research evaluation ,Knowledge management ,media_common.quotation_subject ,MEDLINE ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Bibliometrics ,050905 science studies ,Article ,Task (project management) ,Quality (business) ,Productivity ,media_common ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,business.industry ,Research ,05 social sciences ,General Medicine ,Research Personnel ,Evaluation Studies as Topic ,Metric (unit) ,0509 other social sciences ,050904 information & library sciences ,Citation ,Psychology ,business - Abstract
International audience; Evaluating individual research performance is a complex task that ideally examines productivity, scientific impact, and research quality-a task that metrics alone have been unable to achieve. In January 2011, the French Academy of Sciences published a report on current bibliometric (citation metric) methods for evaluating individual researchers, as well as recommendations for the integration of quality assessment. Here, I draw on key issues raised by this report and comment on the suggestions for improving existing research evaluation practices.
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- 2011
37. In vivo observation of the locomotion of microglial cells in the retina
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Olivier Goupille, Michel Paques, José-Alain Sahel, Manuel Simonutti, Brahim El Mathari, Sébastien Augustin, 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), Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), Alcon, Retina France, Institut Carnot., and Marazova, Katia
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Male ,Scars ,Mice, Transgenic ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Neural tissues ,Biology ,behavioral disciplines and activities ,Retina ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Basal (phylogenetics) ,Mice ,0302 clinical medicine ,In vivo ,Cell Movement ,medicine ,Animals ,Rats, Long-Evans ,030304 developmental biology ,Fluorescent Dyes ,0303 health sciences ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Microscopy, Confocal ,Staining and Labeling ,Anatomy ,humanities ,Confocal scanning laser ophthalmoscopy ,Cell biology ,Rats ,medicine.anatomical_structure ,Neurology ,chemistry ,Microglia ,medicine.symptom ,Early phase ,Indocyanine green ,030217 neurology & neurosurgery - Abstract
This study was funded in part by grants from Alcon, Retina France and the Institut Carnot. M.P. is the recipient of a contract “Interface” from INSERM.; International audience; Microglial cells (MCs) are active sensors and reactive phagocytes of neural tissues. They are known to migrate and accumulate in areas of neuronal damage. Thus, microglial locomotion is an essential feature of the inflammatory reaction in neural tissue. Yet, to our knowledge there has been no report of direct in vivo observation of the migration of MCs. Here, we show that intravitreally injected cyanine dyes (DiO, DiI, and indocyanine green) are sequestrated in MCs during several months, and subsequently in vivo images of these fluorescent MCs can be obtained by confocal scanning laser ophthalmoscopy. This enabled noninvasive, time-lapse observation of the migrating behavior of MCs, both in the basal state and following laser damage. In the basal state, a slow, intermittent, random-like locomotion was observed. Following focal laser damage, MCs promptly (i.e., within 1 h) initiated centripetal, convergent migration. MCs up to 400 μm away migrated into the scar at velocities up to 7 μm/min. This early phase of centripetal migration was followed by a more prolonged phase of nontargeted locomotion around and within injured sites during at least 24 h. Cyanine-positive cells persisted within the scar during several weeks. To our knowledge, this is the first in vivo observation of the locomotion of individual MCs. Our results show that the locomotion of MCs is not limited to translocation to acutely damaged area, but may also be observed in the basal state and after completion of the recruitment of MCs into scars.
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- 2010
38. Current challenges of ophthalmology in France
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Isabelle Audo, Institut de la Vision, 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), 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), and Marazova, Katia
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medicine.medical_specialty ,Telemedicine ,genetic structures ,National Health Programs ,Population ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Article ,03 medical and health sciences ,0302 clinical medicine ,Informed consent ,Ophthalmology ,medicine ,Humans ,Medical prescription ,Practice Patterns, Physicians' ,education ,ComputingMilieux_MISCELLANEOUS ,Preventive healthcare ,education.field_of_study ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,business.industry ,Public health ,Private sector ,eye diseases ,3. Good health ,Private practice ,030221 ophthalmology & optometry ,Workforce ,France ,business ,Delivery of Health Care ,030217 neurology & neurosurgery - Abstract
To comprehend the current challenges that French ophthalmic care is facing, one has first to appreciate the system and the changes that have occurred over the years leading to the current situation. French ophthalmic care is organized differently from its British and American counterparts and resembles its European neighbors. It follows a basic principle of the French medical practice which should guarantee a strict separation of medical care and prescription from commercial sales. Ophthalmologists and orthoptists, provide care to a patient, on one hand. Pharmacists and opticians on the other hand, enter commercial transactions with a client. The ophthalmologist is the center of the ophthalmic care, performing regular ophthalmic examination, prescribing glasses, contact lenses and supervising their tolerance, as well as performing ophthalmic surgery. The French ophthalmologist works closely in relation with orthoptists who can provide additional examinations, such as visual field tests, strabismus or low vision aid rehabilitation and opticians who provide glasses and contact lenses upon medical prescription. French patients are free to choose their practitioner and the National Health Insurance, la Securite Sociale, covers about 70 to 80% of the ophthalmologists and orthoptists fees whereas fees for optics and even more for low vision aid devices have never been well reimbursed and would be covered by optional private insurances. During recent years, optometrists have been trained through schools of optics and masters delivered by 2 scientific universities. However, their status is not well defined by the Health authorities, their potential fees for private consultations resulting in glasses prescription and delivery would not be covered by the National Health Insurance and their role in the scheme of French eye care is a recurrent and often passionate matter of debate. The number of practicing ophthalmologists in France is currently estimated at about 5300 (5354 from the last census reported in 2009 by the French national medical council1). This number has been stable over the past 15 years. Thus, for a general population reaching nearly 63 million, there are fewer than 9 ophthalmologists for 100 000 inhabitants, similar to Germany but lower than other European countries such as Belgium and Czech Republic (10 per 100 000), Italy and Spain (12 per 100 000) or Greece (14 per 100 000).3 Among practicing ophthalmologists, 43.5% are women. In comparison, 38.8% of all medical doctors are female. This percentage is even higher for the age range below 55, corresponding to the feminization of the medical profession.3 About 61% of practicing ophthalmologists are working only in private practice which is usually organized between a private office for ophthalmic examinations and a private clinic for surgical sessions.1 The distribution of these private practitioners across France is not uniform with a higher concentration in metropolitan areas, the Parisian region and the South of France and a real scarcity in rural areas and in Northern France. For the past 15 years, especially in metropolitan areas, the traditional model of a single-ophthalmologist private setting has largely been replaced by practices of 3 or more ophthalmologists, with often complementary expertise, who can appoint a secretary, an accountant, orthoptists and nurses. Some of these offices are equipped with the state-of-the art imaging techniques, visual field testing and even with visual electrophysiology. Group practices create a more favorable financial environment for purchase of modern and expensive equipment. Private offices seldom provide space for outpatient surgery. However, some practices can provide laser treatment, as well as, suitable facilities for photodynamic therapy or intravitreal injections. Such settings provide efficient care competing with public services with often dynamic medical discussions within and around the group similar to teaching hospitals, with the only additional pressure of productivity to repay loans contracted for equipment purchase. Aside from the 61% in private practice, an additional 13% are employed either by small private health centers or public hospitals, including academic centers.1 Moreover, 26% of practicing ophthalmologists work both in private and public practice, often keeping one or 2 clinical or surgical sessions in the hospital where they have been trained.1 The average age of practicing ophthalmologists is 49, with fewer ophthalmologists below 45 than above 55, reflecting the progressive aging of the ophthalmic population and rising concerns for the next 10 to 20 years.3 As the current group of practicing ophthalmologist retires, the number of graduating ophthalmologists each year, which is currently around 80, will not be sufficient to replace retirement and will increased disparity in care coverage, especially in the more sparsely populated areas of France. In fact, the number of ophthalmologist would decrease by 35% during the next 15 years.4 This projection applies not only to ophthalmologists but also to other specialists such as dermatologists and even to general practitioners. Reasons given for this situation include the selective access established in the 1970s to enter medical school and subsequently to enroll in a residency program in the 1980s, resulting in a 50% decrease of ophthalmologists trained per year. On the other hand, ophthalmology faces challenges generated by the increase of the French population, its aging and also the need to implement novel techniques and treatments as well as to establish a workable plan of preventive medicine. Many professionals have rung the alarm for more than 20 years including the National Union of French Ophthalmologists which has been very active in surveying practitioners, promoting debate and proposing solutions to avoid a critical situation.5, 6 Solutions are currently implemented to face the shortage in ophthalmologists and maintain an up-to-date standard of care, with free access to all. The obvious measure has been to gradually increase the number of trained ophthalmologist per year. Ideally, doubling this number within 5 years would ensure an appropriate replacement for retirement and this would only represent an additional 1.5 residents trained per year for each university center.5 Emphasis is also given on improving surgical training with a plan to add a year to ophthalmology residency, passing it from 4 to 5 years. This measure would ensure a sufficient number of well-trained ophthalmic surgeons to serve the additional load of cataract surgery generated by aging of the population. In addition, despite the absence of postgraduate recertification in France, the health ministry has implemented a mandatory requirement for post-university training in 2001.7,8 Furthermore, the French Ophthalmology Society with the National Union of French Ophthalmologists have produced guidelines on good ophthalmological practice, procedures and example of informed consent forms for special ophthalmic procedures.9,10 Although these documents have no legal standing, they are valuable in informing and helping ophthalmologists to keep an up-to-date practice. To ensure better geographical distribution of care, local initiatives have been proposed and encouraged. Some local authorities are providing free office space, surgical facilities as well as facilitating housing and support for young ophthalmologists. In addition, a new status of replacing practitioner, medecin remplacant, is created to encourage mobility for ophthalmologists unwilling to establish a permanent practice and flexible enough to adapt their activities toward available locum work. Furthermore, well-qualified ophthalmologists from other European countries with no shortage of ophthalmologists have been encouraged to come and practice in France. Along with increasing the number of ophthalmologists, the other efforts has been to increase the training and recruitment of orthoptists, the “historical partners” of French ophthalmologists and increase the number of tasks that could be delegated to them under medical supervision.11 For the vast majority of French ophthalmologists, this would be the best solution and more logical than introducing a new partner, the optometrist, within the French ophthalmic landscape. In addition, further efforts have been made to reinforce cooperation between the public and private sector and encourage the creation of health networks oriented toward preventive medicine with the help of telemedicine and mobile ophthalmic units. In collaboration with local ophthalmologists and often at their initiative, campaigns have been organized to improve early diagnosis of glaucoma, diabetic retinopathy, AMD and child amblyopia. Such campaigns are particularly relevant in regions with low ophthalmic coverage. With the aging of the population and the increase of AMD prevalence, efforts are also given to low vision aid rehabilitation. Orthoptists and opticians would be major players in these efforts. The future will reveal if these measures will be sufficient to fulfill the overall objectives of eye care in France: to ensure an available and transparent system for the patient, to provide ethical care free from conflict of interest, to create an efficient prevention strategy within a coherent public health system, and to moderate the economic cost for the best coverage of entire population.
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- 2010
39. Expression of rod-derived cone viability factor: dual role of CRX in regulating promoter activity and cell-type specificity
- Author
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Marie Laure Niepon, Donald J. Zack, Sophie Lambard, Olivier Goureau, Cynthia A. Berlinicke, Thierry Léveillard, José-Alain Sahel, Sacha Reichman, Institut de la Vision, 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), Department of Molecular Biology and Genetics, Department of Neuroscience, and Institute of Genetic Medicine, Johns Hopkins University School of Medicine, 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), and Marazova, Katia
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Transcription, Genetic ,Sequence analysis ,Green Fluorescent Proteins ,Molecular Sequence Data ,lcsh:Medicine ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Biology ,Cell Line ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Thioredoxins ,Gene expression ,Animals ,Humans ,Luciferase ,nucleoredoxin-like genes NXNL1 and NXNL2 ,Binding site ,Promoter Regions, Genetic ,lcsh:Science ,Gene ,030304 developmental biology ,Sequence Deletion ,Homeodomain Proteins ,0303 health sciences ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Multidisciplinary ,Base Sequence ,HEK 293 cells ,lcsh:R ,Promoter ,Genetics and Genomics/Gene Expression ,DNA ,Molecular Biology/Transcription Initiation and Activation ,Molecular biology ,Rod-Derived Cone Viability Factor ,Retinitis pigmentosa ,Electroporation ,Regulatory sequence ,Trans-Activators ,Ophthalmology/Retinal Disorders ,Electrophoresis, Polyacrylamide Gel ,lcsh:Q ,sense organs ,030217 neurology & neurosurgery ,Research Article - Abstract
International audience; BACKGROUND: RdCVF and RdCVF2, encoded by the nucleoredoxin-like genes NXNL1 and NXNL2, are trophic factors with therapeutic potential that are involved in cone photoreceptor survival. Studying how their expression is regulated in the retina has implications for understanding both their activity and the mechanisms determining cell-type specificity within the retina. METHODOLOGY/PRINCIPAL FINDINGS: In order to define and characterize their promoters, a series of luciferase/GFP reporter constructs that contain various fragments of the 5'-upstream region of each gene, both murine and human, were tested in photoreceptor-like and non-photoreceptor cell lines and also in a biologically more relevant mouse retinal explant system. For NXNL1, 5'-deletion analysis identified the human -205/+57 bp and murine -351/+51 bp regions as having promoter activity. Moreover, in the retinal explants these constructs drove expression specifically to photoreceptor cells. For NXNL2, the human -393/+27 bp and murine -195/+70 bp regions were found to be sufficient for promoter activity. However, despite the fact that endogenous NXNL2 expression is photoreceptor-specific within the retina, neither of these DNA sequences nor larger upstream regions demonstrated photoreceptor-specific expression. Further analysis showed that a 79 bp NXNL2 positive regulatory sequence (-393 to 315 bp) combined with a 134 bp inactive minimal NXNL1 promoter fragment (-77 to +57 bp) was able to drive photoreceptor-specific expression, suggesting that the minimal NXNL1 fragment contains latent elements that encode cell-type specificity. Finally, based on bioinformatic analysis that suggested the importance of a CRX binding site within the minimal NXNL1 fragment, we found by mutation analysis that, depending on the context, the CRX site can play a dual role. CONCLUSIONS/SIGNIFICANCE: The regulation of the Nucleoredoxin-like genes involves a CRX responsive element that can act as both as a positive regulator of promoter activity and as a modulator of cell-type specificity.
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- 2010
40. The disruption of the rod-derived cone viability gene leads to photoreceptor dysfunction and susceptibility to oxidative stress
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Marie-Laure Niepon, Serge Picaud, Andranik Petrosian, Céline Jaillard, Thierry Léveillard, Emmanuelle Clérin, Olivier Poch, Irene Lee-Rivera, Wolfgang Raffelsberger, Bernd Kinzel, Therese Cronin, José-Alain Sahel, Institut de la Vision, 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), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Novartis Pharma AG, Bunatian Institute of Biochemistry [Yerevan, Armenia] (BIB), Marazova, Katia, RETinal Training NETwork - INCOMING, 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), 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), Bunatian Institute of Biochemistry, ANR Maladies rares, This work was supported by Inserm, the European commission (RETinal Training NETwork), ANR Maladies rares 2006 Grant and FFB USA., European Project, Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Louis Pasteur - Strasbourg I, and Novartis Pharma AG [Basel, Switzerland]
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genetic structures ,[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology ,Apoptosis ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,[SDV.BC.BC]Life Sciences [q-bio]/Cellular Biology/Subcellular Processes [q-bio.SC] ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Thioredoxins ,Retinal Rod Photoreceptor Cells ,injury response ,Genetics ,Mice, Knockout ,0303 health sciences ,Cell biology ,medicine.anatomical_structure ,Retinal Cone Photoreceptor Cells ,Fibroblast Growth Factor 2 ,neuroprotection ,Erg ,microarray ,Signal Transduction ,Programmed cell death ,Biology ,Article ,Retina ,03 medical and health sciences ,Retinitis pigmentosa ,medicine ,Animals ,Outer nuclear layer ,Eye Proteins ,Molecular Biology ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Gene Expression Profiling ,Retinal ,[SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology ,Cell Biology ,thioredoxin ,medicine.disease ,eye diseases ,Oxidative Stress ,chemistry ,030221 ophthalmology & optometry ,retinal degeneration ,Lipid Peroxidation ,sense organs - Abstract
International audience; Rod-derived cone viability factor (RdCVF) is a thioredoxin-like protein, which has therapeutic potential for rod-cone dystrophies such as retinitis pigmentosa (RP). Cone loss in rodent models of RP is effectively reduced by RdCVF treatment. In this study, we investigate the physiological role of RdCVF in the retina by analyzing the phenotype of the mouse lacking the RdCVF gene, Nxnl1. Although the mice do not show an obvious developmental defect, an age-related reduction of both cone and rod function and a delay in the dark-adaptation of the retina are recorded by electroretinogram (ERG). This functional change is accompanied by a 17% reduction in cone density and a 20% reduction in thickness of the outer nuclear layer. The transcriptome of the retina reveals early changes in the expression of genes involved in programmed cell death, stress-response and redox-signaling, which is followed by a generalized injury response with increased microglial activation, GFAP, FGF2 and lipid peroxidation levels. Furthermore, cones of the mice lacking Nxnl1 are more sensitive to oxidative stress with a reduction of 65% in the cone flicker ERG amplitude measured under hyperoxic conditions. We show here that the RdCVF gene, in addition to therapeutic properties, has an essential role in photoreceptor maintenance and resistance to retinal oxidative stress.
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- 2010
41. Genetic reactivation of cone photoreceptors restores visual responses in retinitis pigmentosa
- Author
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Erik Cabuy, Jens Duebel, Michel Paques, José-Alain Sahel, Valérie Forster, Martin Biel, Botond Roska, Peter Humphries, Didier Trono, Mathias Fradot, D. Balya, Serge Picaud, Karl Deisseroth, Sandra Siegert, Mathias W. Seeliger, Saddek Mohand-Said, Volker Busskamp, Anna C. Groner, Tim J. Viney, 'Frontiers in Genetics' program, Ecole Polytechnique Fédérale de Lausanne (EPFL)-National Center of Competence in Research, Neural Circuit Laboratories, Friedrich Miescher Institute for Biomedical Research, 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), School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), Diagnostics Research Group, Eberhard-Karls University, Center for Integrated Protein Science (CIPSM), Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig-Maximilians-Universität München (LMU)-Helmholtz Zentrum München = German Research Center for Environmental Health, Smurfit Institute of Genetics, Trinity College Dublin, Fondation Ophtalmologique Adolphe de Rothschild [Paris], Department of Bioengineering, Department of Psychiatry and Behavioral Sciences, Stanford University, Friedrich Miescher Institute, US Office of Naval Research Naval International Cooperative Opportunities in Science and Technology Program grant, Foundation Fighting Blindness (USA), Swiss National Science Foundation, National Centers of Competence in Research Frontiers in Genetics, ANR-07-TECS-0014,MEDINAS,Matrices d'Electrodes en Diamant pour l'Interfaçage Neuronal Appliqué à la Suppléance fonctionnelle (MEDINAS)(2007), European Project, Fondation Ophtalmologique Adolphe de Rothschild, Marazova, Katia, Technologies pour la santé - Matrices d'Electrodes en Diamant pour l'Interfaçage Neuronal Appliqué à la Suppléance fonctionnelle (MEDINAS) - - MEDINAS2007 - ANR-07-TECS-0014 - TECSAN - VALID, Marie Curie Excellence Grant, EU HEALTH-F2- 223156, RETICIRC - INCOMING, Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Ludwig Maximilian University of Munich [Germany] (LMU München)-Helmholtz-Zentrum München (HZM), 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 Technische Universität Munchen - Université Technique de Munich [Munich, Allemagne] (TUM)-Helmholtz-Zentrum München (HZM)-Ludwig Maximilian University of Munich [Germany] (LMU München)
- Subjects
Retinal degeneration ,Retinal Ganglion Cells ,MESH: Evoked Potentials, Visual ,genetic structures ,Light ,Serotypes ,Expression ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,MESH: Dependovirus ,MESH: Mice, Knockout ,Tissue Culture Techniques ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,MESH: Genetic Vectors ,MESH: Animals ,Selectivity ,Promoter Regions, Genetic ,Halorhodopsin ,Mice, Knockout ,0303 health sciences ,Multidisciplinary ,Halobacteriaceae ,Visually guided ,MESH: Retina ,Retinal Degeneration ,Anatomy ,Dependovirus ,3. Good health ,medicine.anatomical_structure ,Retinal Cone Photoreceptor Cells ,Halorhodopsins ,Retinitis Pigmentosa ,Visual phototransduction ,MESH: Halorhodopsins ,Movement ,Genetic Vectors ,Biology ,Transfection ,Retina ,03 medical and health sciences ,MESH: Halobacteriaceae ,Retinitis pigmentosa ,MESH: Promoter Regions, Genetic ,medicine ,Animals ,Humans ,Visual Pathways ,MESH: Tissue Culture Techniques ,MESH: Vision, Ocular ,MESH: Mice ,Vision, Ocular ,030304 developmental biology ,MESH: Visual Pathways ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,Blindness ,MESH: Transfection ,Ganglion-Cells ,Retinal ,MESH: Retinal Ganglion Cells ,Genetic Therapy ,medicine.disease ,MESH: Light ,eye diseases ,Disease Models, Animal ,MESH: Retinal Cone Photoreceptor Cells ,chemistry ,Direction ,MESH: Retinitis Pigmentosa ,Evoked Potentials, Visual ,sense organs ,MESH: Disease Models, Animal ,MESH: Gene Therapy ,Neuroscience ,030217 neurology & neurosurgery ,Model - Abstract
Let There Be Light Retinitis pigmentosa, a disease that can result from a wide variety of genetic defects, causes degeneration of photoreceptor cells in the retina and leads to blindness. In the course of the disease, it is generally the rod photoreceptor cells that degenerate first. Cone photoreceptor cells may persist, but in a damaged and nonfunctional state. Busskamp et al. (p. 413 , published online 24 June; see the cover; see the Perspective by Cepko ) have now applied a gene therapy approach to mouse models of retinitis pigmentosa. Inducing expression of a bacterial light-activated ion pump, halorho dopsin, in the damaged cone cells improved visual responses in the diseased mouse retinas. Thus, it may be possible to rescue cone photoreceptors therapeutically, even after they have already been damaged.
- Published
- 2010
42. Rod-Derived Cone Viability Factor for Treating Blinding Diseases: From Clinic to Redox Signaling
- Author
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Thierry Léveillard, José-Alain Sahel, 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), Service du professeur Sahel, Centre hospitalier national d'ophtalmologie des 15-20, Institute of Ophthalmology, University College of London [London] (UCL), Fondation Ophtalmologique Adolphe de Rothschild, Inserm, UPMC, Retina France, Fédération de aveugles de France, Foundation Fighting Blindness, Novartis, Fovea Pharma, European Project, Marazova, Katia, EVI-GENORET (FP6) - INCOMING, and Fondation Ophtalmologique Adolphe de Rothschild [Paris]
- Subjects
Retinal degeneration ,Retinal Disorder ,genetic structures ,Cell Survival ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Biology ,Blindness ,medicine.disease_cause ,Retinal Cone Photoreceptor Cells ,Neuroprotection ,Article ,Translational Research, Biomedical ,Mice ,03 medical and health sciences ,Thioredoxins ,0302 clinical medicine ,Retinal Diseases ,Retinal Rod Photoreceptor Cells ,medicine ,Animals ,Humans ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,0303 health sciences ,Retina ,Retinal Degeneration ,General Medicine ,medicine.disease ,Cell biology ,Oxidative Stress ,medicine.anatomical_structure ,030221 ophthalmology & optometry ,sense organs ,Signal transduction ,Oxidation-Reduction ,Oxidative stress ,Signal Transduction - Abstract
International audience; The identification of one mechanism that causes vision loss in inherited degenerative retinal disorders revealed a new signaling molecule that represents a potential therapy for these currently untreatable diseases. This protein, called rod-derived cone viability factor (RdCVF), maintains the function and consequently the viability of cone photoreceptor cells in the retina; mice that lack this factor exhibit a progressive loss of photoreceptor cells. The gene encoding RdCVF also encodes, by differential splicing, a second product that has characteristics of a thioredoxin-like enzyme and protects both photoreceptor cells and, more specifically, its interacting protein partner, the tau protein, against oxidative damage. This signaling pathway potentially links environmental insults to an endogenous neuroprotective response.
- Published
- 2010
43. The homeobox gene CHX10/VSX2 regulates RdCVF promoter activity in the inner retina
- Author
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Sophie Lambard, Sacha Reichman, Raymond Ripp, Najate Aït-Ali, Thierry Léveillard, Ravi Kiran Reddy Kalathur, Yanjiang Yang, Olivier Poch, Donald J. Zack, Aurélie Lardenois, José-Alain Sahel, 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), 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), Wilmer Ophthalmological Institute, Johns Hopkins University School of Medicine, ANR Chaire d'excellence, This work was supported by Inserm, CIFRE, ANR Chaire d'excellence, NIH, and EVI-GENORET., European Project: 29850,EVI-GENORET, 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), Marazova, Katia, and Functional Genomics of the Retina in Health and Disease - EVI-GENORET - 29850 - OLD
- Subjects
genetic structures ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,MESH: Mice, Knockout ,Mice ,0302 clinical medicine ,Thioredoxins ,MESH: Thioredoxins ,MESH: Eye Proteins ,MESH: Animals ,Promoter Regions, Genetic ,Genetics (clinical) ,Regulation of gene expression ,Zinc finger ,Mice, Knockout ,0303 health sciences ,Mice, Inbred BALB C ,MESH: Retina ,Genes, Homeobox ,General Medicine ,Transfection ,Articles ,MESH: Transcription Factors ,MESH: Gene Expression Regulation ,medicine.anatomical_structure ,Retinitis Pigmentosa ,Protein Binding ,MESH: Mice, Inbred BALB C ,Biology ,Retina ,03 medical and health sciences ,Retinitis pigmentosa ,MESH: Homeodomain Proteins ,MESH: Promoter Regions, Genetic ,Genetics ,medicine ,Animals ,Humans ,MESH: Protein Binding ,Eye Proteins ,Molecular Biology ,Transcription factor ,MESH: Mice ,030304 developmental biology ,Homeodomain Proteins ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,MESH: Genes, Homeobox ,medicine.disease ,Molecular biology ,eye diseases ,Gene Expression Regulation ,Homeobox ,PAX4 ,MESH: Retinitis Pigmentosa ,sense organs ,030217 neurology & neurosurgery ,Transcription Factors - Abstract
International audience; Rod-derived Cone Viability Factor (RdCVF) is a trophic factor with therapeutic potential for the treatment of retinitis pigmentosa, a retinal disease that commonly results in blindness. RdCVF is encoded by Nucleoredoxin-like 1 (Nxnl1), a gene homologous with the family of thioredoxins that participate in the defense against oxidative stress. RdCVF expression is lost after rod degeneration in the first phase of retinitis pigmentosa, and this loss has been implicated in the more clinically significant secondary cone degeneration that often occurs. Here, we describe a study of the Nxnl1 promoter using an approach that combines promoter and transcriptomic analysis. By transfection of selected candidate transcription factors, chosen based upon their expression pattern, we identified the homeodomain proteins CHX10/VSX2, VSX1 and PAX4, as well as the zinc finger protein SP3, as factors that can stimulate both the mouse and human Nxnl1 promoter. In addition, CHX10/VSX2 binds to the Nxnl1 promoter in vivo. Since CHX10/VSX2 is expressed predominantly in the inner retina, this finding motivated us to demonstrate that RdCVF is expressed in the inner as well as the outer retina. Interestingly, the loss of rods in the rd1 mouse, a model of retinitis pigmentosa, is associated with decreased expression of RdCVF by inner retinal cells as well as by rods. Based upon these results, we propose an alternative therapeutic strategy aimed at recapitulating RdCVF expression in the inner retina, where cell loss is not significant, to prevent secondary cone death and central vision loss in patients suffering from retinitis pigmentosa.
- Published
- 2010
44. Functional cone rescue by RdCVF protein in a dominant model of retinitis pigmentosa
- Author
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Serge Picaud, Emmanuelle Clérin, José-Alain Sahel, Saddek Mohand-Said, Thierry Léveillard, Ying Yang, Valérie Fontaine, Manuel Simonutti, Aude Danan, Laboratoire de Physiopathologie Cellulaire et Moleculaire de la Retine, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service du Pr Sahel, Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts (CHNO), 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), Institute of Ophthalmology, University College of London [London] (UCL), Fondation Ophtalmologique Adolphe de Rothschild [Paris], This work was supported by Inserm, EVI-GENORET and Foundation Fighting Blindness (USA)., European Project: 29850,EVI-GENORET, Fondation Ophtalmologique A. de Rothschild, Marazova, Katia, and Functional Genomics of the Retina in Health and Disease - EVI-GENORET - 29850 - OLD
- Subjects
MESH: Cell Death ,genetic structures ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,MESH: Amino Acid Sequence ,MESH: Rats, Sprague-Dawley ,MESH: Base Sequence ,MESH: Electroretinography ,Photoreceptor cell ,Rats, Sprague-Dawley ,Mice ,Thioredoxins ,0302 clinical medicine ,MESH: Thioredoxins ,MESH: Reverse Transcriptase Polymerase Chain Reaction ,Drug Discovery ,MESH: Animals ,Rod cell ,Genetics ,0303 health sciences ,Cell Death ,medicine.diagnostic_test ,biology ,Reverse Transcriptase Polymerase Chain Reaction ,MESH: Retina ,MESH: Gene Expression Regulation ,Cell biology ,medicine.anatomical_structure ,Rhodopsin ,Retinal Cone Photoreceptor Cells ,Molecular Medicine ,Rats, Transgenic ,Retinitis Pigmentosa ,MESH: Rats ,Molecular Sequence Data ,MESH: Sequence Alignment ,Retina ,03 medical and health sciences ,Retinitis pigmentosa ,Electroretinography ,medicine ,Animals ,Humans ,Amino Acid Sequence ,Molecular Biology ,MESH: Mice ,030304 developmental biology ,Pharmacology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,MESH: Humans ,MESH: Molecular Sequence Data ,Base Sequence ,Original Articles ,medicine.disease ,Cone cell ,Rats ,Transplantation ,MESH: Retinal Cone Photoreceptor Cells ,Gene Expression Regulation ,MESH: Rats, Transgenic ,030221 ophthalmology & optometry ,biology.protein ,MESH: Retinitis Pigmentosa ,sense organs ,Sequence Alignment - Abstract
International audience; In retinitis pigmentosa (RP), a majority of causative mutations affect genes solely expressed in rods; however, cone degeneration inevitably follows rod cell loss. Following transplantation and in vitro studies, we demonstrated the role of photoreceptor cell paracrine interactions and identified a Rod-derived Cone Viability Factor (RdCVF), which increases cone survival. In order to establish the clinical relevance of such mechanism, we assessed the functional benefit afforded by the injection of this factor in a frequent type of rhodopsin mutation, the P23H rat. In this model of autosomal dominant RP, RdCVF expression decreases in parallel with primary rod degeneration, which is followed by cone loss. RdCVF protein injections induced an increase in cone cell number and, more important, a further increase in the corresponding electroretinogram (ERG). These results indicate that RdCVF can not only rescue cones but also preserve significantly their function. Interestingly, the higher amplitude of the functional versus the survival effect of RdCVF on cones indicates that RdCVF is acting more directly on cone function. The demonstration at the functional level of the therapeutic potential of RdCVF in the most frequent of dominant RP mutations paves the way toward the use of RdCVF for preserving central vision in many RP patients.
- Published
- 2009
45. Spectrum of Rhodopsin Mutations in French Autosomal Dominant Rod–Cone Dystrophy Patients
- Author
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Gaël Manes, Shomi S. Bhattacharya, Veselina Moskova-Doumanova, Christian P. Hamel, José-Alain Sahel, Saddek Mohand-Said, Isabelle Audo, Xavier Zanlonghi, Marie-Elise Lancelot, Olivier Poch, Anne Friedrich, Aline Antonio, Christina Zeitz, 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), Department of Molecular Genetics, Institute of Ophthalmology, Physiopathologie et thérapie des déficits sensoriels et moteurs, Université Montpellier 2 - Sciences et Techniques (UM2)-IFR76-Institut National de la Santé et de la Recherche Médicale (INSERM), 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), Service Exploration Fonctionnelle de la Vision, Clinique Sourdille, Centre de référence des affections sensorielles d'origine génétique, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui De Chaulliac, The project was financially supported by Foundation Fighting Blindness (I.A.), Foundation Voir et Entendre and BQR, Université Pierre et Marie Curie6 (C.Z), PHRC national adRP (C H)., Marazova, Katia, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], and Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
- Subjects
Male ,Retinal degeneration ,genetic structures ,DNA Mutational Analysis ,Visual Acuity ,[SDV.GEN] Life Sciences [q-bio]/Genetics ,Gene mutation ,medicine.disease_cause ,Polymerase Chain Reaction ,0302 clinical medicine ,Prevalence ,Fluorescein Angiography ,Child ,Genes, Dominant ,Genetics ,0303 health sciences ,Mutation ,biology ,Middle Aged ,Pedigree ,3. Good health ,Phenotype ,Rhodopsin ,Female ,France ,Retinitis Pigmentosa ,Tomography, Optical Coherence ,Photoreceptor Cells, Vertebrate ,Adult ,Adolescent ,Genotype ,White People ,Article ,Young Adult ,03 medical and health sciences ,Retinitis pigmentosa ,Electroretinography ,medicine ,Rod-cone dystrophy ,Humans ,030304 developmental biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Genetic heterogeneity ,Point mutation ,medicine.disease ,eye diseases ,030221 ophthalmology & optometry ,biology.protein ,sense organs - Abstract
Rod-cone dystrophies, also called retinitis pigmentosa (RP), are a clinically and genetically heterogeneous group of inherited retinal disorders primarily affecting rods with secondary cone degeneration 1. RP patients initially often complain of night blindness. This is attributed to the primarily affected rods and clinical sign of the impaired rod function. Later on, when the secondary cone dysfunctions manifests, progressive visual field constriction, abnormal color vision and loss of central vision can be observed – signs of decreasing cone function. As the disease progresses and retinal dysfunction decreases, visual impairment increases: in some cases the disease may eventually result in very severe visual impairment or even blindness. RP is the most common inherited form of severe retinal degeneration, with a frequency of about 1 in 4000 births and more than 1 million affected individuals over the world. The mode of inheritance can be X-linked (5–15%) autosomal dominant (30–40%) or autosomal recessive (50–60%) The remaining patients represent isolated cases of which the inheritance trait can not be established 1. To date, 20 autosomal dominant RP (adRP) genes have been reported (http://www.sph.uth.tmc.edu/Retnet/). One of the major genes underlying this disorder is rhodopsin (RHO) coding for the light absorbing molecule that initiates the signal transmission cascade in rod photoreceptors. According to the literature, RHO mutation prevalence ranges from 0 to 50% cases of adRP in cohorts from various geographical origins, with higher numbers reported in the United States 2–18. The genetic and phenotypic heterogeneity is not only found in RP in general but also specifically reflected in adRP with RHO mutations: Over 120 mutations have been identified in different sites of the gene including specific hot spots (http://www.sph.uth.tmc.edu/Retnet/, http://www.hgmd.cf.ac.uk/ac/all.php, http://www.retina-international.org/sci-news/rhomut.htm) 19. Certain mutations in RHO lead to diffuse rod-cone dysfunction whereas other cases are implicated in a more restricted disease that may predominate in the inferior part of the retina such as in sector RP 20. Phenotypic classifications have been proposed to reflect this variability. In particular, Cideciyan and co-workers have distinguished two classes of disease expression with allele-specificity 21: class A mutants show severely generalized abnormal rod function early in life with a constant rate of cone disease progression across the retina with time. Class B mutants show more restricted disease and absent or lateonset night blindness. Other classifications have been proposed based on the underlying pathogenic mechanism involved in adRP due to RHO mutations. Mendes and co-workers classified the different types of mutations in 6 groups. Class I refers exclusively to rhodopsin mutations that fold correctly but are not transported to the outer segment. Class II, refers to mutations that misfold, are retained in the endopasmic reticulum (ER) and cannot easily reconstitute with 11-cis-retinal. Class III refers to mutations that affect endocytosis. Class IV mutations do not affect folding per se but might affect rhodopsin stability and posttranslational modification. Similarly, Class V mutations have no obvious folding defect but show an increased activation rate for transducin. Mutants that appear to fold correctly but lead to the constitutive activation of opsin in the absence of the chromophore and in the dark constitute Class VI. Other mutations with unclear biochemical or cellular defect, or uninvestigated defect were not classified 19. Our comprehensive study presented herein aim to investigate in detail a French adRP cohort coming from 2 different clinical centers, namely Quinze-Vingts hospital in Paris and the Centre Hospitalier Regional in Montpellier located in the south of France. We will present the prevalence of rhodopsin mutations in this cohort and show precise phenotype-genotype correlations. Novel mutations will be analyzed on its predicted pathogenic mechanism as well as frequently mutated sites will be presented as putative candidates for therapeutic approaches.
- Published
- 2010
46. Clinical characteristics and current therapies for inherited retinal degenerations.
- Author
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Sahel JA, Marazova K, and Audo I
- Subjects
- Animals, Bardet-Biedl Syndrome genetics, Choroideremia genetics, Clinical Trials as Topic, Color Vision Defects genetics, Disease Models, Animal, Eye Diseases, Hereditary genetics, Genetic Diseases, X-Linked genetics, Genetic Heterogeneity, Genetic Therapy, Humans, Leber Congenital Amaurosis genetics, Macular Degeneration genetics, Myopia genetics, Night Blindness genetics, Optogenetics, Retinal Degeneration genetics, Retinal Degeneration pathology, Retinal Degeneration therapy
- Abstract
Inherited retinal degenerations (IRDs) encompass a large group of clinically and genetically heterogeneous diseases that affect approximately 1 in 3000 people (>2 million people worldwide) (Bessant DA, Ali RR, Bhattacharya SS. 2001. Molecular genetics and prospects for therapy of the inherited retinal dystrophies. Curr Opin Genet Dev 11: 307-316.). IRDs may be inherited as Mendelian traits or through mitochondrial DNA, and may affect the entire retina (e.g., rod-cone dystrophy, also known as retinitis pigmentosa, cone dystrophy, cone-rod dystrophy, choroideremia, Usher syndrome, and Bardet-Bidel syndrome) or be restricted to the macula (e.g., Stargardt disease, Best disease, and Sorsby fundus dystrophy), ultimately leading to blindness. IRDs are a major cause of severe vision loss, with profound impact on patients and society. Although IRDs remain untreatable today, significant progress toward therapeutic strategies for IRDs has marked the past two decades. This progress has been based on better understanding of the pathophysiological pathways of these diseases and on technological advances., (Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.)
- Published
- 2014
- Full Text
- View/download PDF
47. Dry age-related macular degeneration: A currently unmet clinical need.
- Author
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Girmens JF, Sahel JA, and Marazova K
- Abstract
Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD. Increased understanding of the complex mechanisms that underlie dry AMD will help to address this largely unmet clinical need.
- Published
- 2012
- Full Text
- View/download PDF
48. Whipple's disease.
- Author
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Marazova, Katia, M.D., Ph.D
- Subjects
Whipple's disease ,Malabsorption syndromes ,Lipodystrophy - Abstract
Whipple’s disease is a rare, chronic, systemic infection caused by a gram-positive actinomycete, Tropheryma whipplei .
- Published
- 2023
49. Morgellons disease.
- Author
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Marazova, Katia, MD, PhD
- Subjects
Morgellons disease ,Delusional parasitosis ,Psychoses ,Psychosomatic disorders ,Skin diseases - Abstract
ANATOMY OR SYSTEM AFFECTED: Psychic-emotional system, skin
- Published
- 2024
50. Sporotrichosis.
- Author
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Marazova, Katia, M.D., Ph.D
- Subjects
Communicable diseases ,Sporotrichosis ,Mycoses - Abstract
Sporotrichosis is an infectious disease caused by the soil fungus Sporothrix schenckii that usually affects the skin. Sporotrichosis is commonly acquired through cutaneous inoculation. In rare cases, it can be inhaled. It is not spread from person to person, but zoonotic transmission from infected animals (such as cats and horses) is possible.
- Published
- 2023
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