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151. Debate on Germline Gene Editing

Author

Cartier-Lacave, Nathalie, primary, Ali, Robin, additional, Ylä-Herttuala, Seppo, additional, Kato, Kazuto, additional, Baetschi, Bernard, additional, Lovell-Badge, Robin, additional, Naldini, Luigi, additional, and Thrasher, Adrian, additional

Published
2016
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153. 256. A Novel Rationally Designed AAV Capsid Yields a Potent Neurotropic Gene Therapy Vector

Author

Henckaerts, Els, primary, Tordo, Julie, additional, Palomar, Nuria, additional, Rahman, Jahedur, additional, Aldrin-Kirk, Patrick, additional, Basche, Mark, additional, Bennett, Antonette, additional, O'Leary, Claire, additional, Ali, Robin, additional, Agbandje-McKenna, Mavis, additional, Bigger, Brian, additional, Rahim, Ahad A., additional, Björklund, Tomas, additional, Waddington, Simon, additional, and Linden, R. Michael, additional

Published
2016
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154. Myeloid-Derived Vascular Endothelial Growth Factor and Hypoxia-Inducible Factor Are Dispensable for Ocular Neovascularization—Brief Report

Author

Liyanage, Sidath E., primary, Fantin, Alessandro, additional, Villacampa, Pilar, additional, Lange, Clemens A., additional, Denti, Laura, additional, Cristante, Enrico, additional, Smith, Alexander J., additional, Ali, Robin R., additional, Luhmann, Ulrich F., additional, Bainbridge, James W., additional, and Ruhrberg, Christiana, additional

Published
2016
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156. DIY eye: generation of complex organs in vitro is a major challenge in regenerative medicine. But it is not an impossible one: an entire synthetic retina has now been generated from embryonic stem cells

Author

Ali, Robin R. and Sowden, Jane C.

Subjects
Retina -- Physiological aspects -- Research, Embryonic stem cells -- Research -- Physiological aspects, Regenerative medicine -- Research -- Physiological aspects, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

In this issue, Eiraku et al. (1) provide a series of extraordinary videos recording the formation of an embryonic mouse eye: for the first time, we see unfolding in real [...]

Published
2011

157. Evaluating soil degradation under different scenarios of agricultural land management in Mediterranean region

Author

Abd-Elmabod, S.K., Ali, Robin R., Anaya Romero, María, Jordán, A., Muñoz Rojas, M., Abdelmageed, T. A., Martínez Zavala, L., and Rosa, Diego de la

Subjects
MicroLEIS decision support system, Soils, Egypt, Contamination risks, Pantanal model, El-Fayoum province
Abstract

14 pages, 9 figures, 7 tables, 30 references., In this research work the Agro-Ecological Decision Support System MicroLEIS DSS, was applied to evaluate land degradation under different scenarios of land management. El-Fayoum depression was selected as a pilot area, this is one of the western desert depressions in the Arab Republic of Egypt. The area offers a great potential for agriculture using water from the river Nile. The main objective is to investigate and predict the risk of soil contamination for phosphorus, nitrogen, heavy metals and pesticides under traditional and recommended management scenarios of maize cultivation. The following components of MicroLEIS DSS have been used: 1) soil database (SDBm), 2) agro-climate database (CDBm), 3) agricultural management database (MDBm), and 4) the specific assessment model for the vulnerability of soil contamination called “Pantanal”. Then, a recommended scenario based on different land management has been produced for maize crop, which aimed to reduce soil contamination vulnerability of phosphorus, nitrogen, heavy metals and pesticides. The model application results are grouped in five vulnerability classes: V1 (none), V2 (low), V3 (moderate), V4 (high) and V5 (extreme) for each specific contaminant. Results obtained for El-Fayoum area showed that 47.8% and 52.2% of total studied area were classified as V3 and V4 vulnerable land due to phosphorus contamination under the traditional management scenario, but 41.9%5.9% and 52% of total area were classified as V2, V3 and V4 because of the same contaminate under recommended management scenario. On the other hand, 98.7% and 1.3% of the total area were classified as V3 and V4 vulnerable land due to nitrogen and heavy metals under the traditional management scenario, however in the other recommended scenario 94.0% and 5.6% were classified as V1 and V2 classes due to nitrogen contaminate and 79.0%, 19.1% and 1.7% were classified as V1, V2 and V4 for heavy metals contaminates. In the same trend 2.6%, 8.1%, 17.4% and 91.7% were classified as V1, V3, V4 and V5 due to pesticides contamination in the actual management scenario, however 24.0% and 76.0% were classified as V1 and V2 respectively due to the same contaminant under the recommended management scenario. In summary, we can ensure that these innovative agro-ecological studies such as those developed by MicroLEIS DSS can be applied and adapted in the agricultural provinces of Egypt in order to achieve a national sustainable rural management

Published
2012

158. Impact of topography and soil factors on crop suitability in two Mediterranean areas (Egypt and Spain)

Author

Abd-Elmabod, S.K., Jordán, A., Anaya Romero, María, Ali, Robin R., Muñoz Rojas, M., Martínez Zavala, L., and Rosa, Diego de la

Abstract

Comunicación oral presentada al European Geosciences Union General Assembly 2012, que tuvo lugar del 22-27, abril 2012, en Viena, Austria., The aim of this research is to study the influence of topography and soil factors on crop suitability two Mediterranean areas: Sevilla (southern Spain) and El-Fayoum (northern Egypt).

Published
2012

159. Spectral sensitivity measurements reveal partial success in restoring missing rod function with gene therapy

Author

Ripamonti, Caterina, primary, Henning, G. Bruce, additional, Robbie, Scott J., additional, Sundaram, Venki, additional, van den Born, L. Ingeborgh, additional, Casteels, Ingele, additional, de Ravel, Thomy J. L., additional, Moore, Anthony T., additional, Smith, Alexander J., additional, Bainbridge, James W., additional, Ali, Robin R., additional, and Stockman, Andrew, additional

Published
2015
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160. Transplantation of Photoreceptor Precursors Isolated via a Cell Surface Biomarker Panel from Embryonic Stem Cell-Derived Self-Forming Retina

Author

Lakowski, Jorn, primary, Gonzalez-Cordero, Anai, additional, West, Emma L., additional, Han, Ya-Ting, additional, Welby, Emily, additional, Naeem, Arifa, additional, Blackford, Samuel J. I., additional, Bainbridge, James W. B., additional, Pearson, Rachael A., additional, Ali, Robin R., additional, and Sowden, Jane C., additional

Published
2015
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163. Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179

Author

Nishiguchi, Koji M., primary, Carvalho, Livia S., additional, Rizzi, Matteo, additional, Powell, Kate, additional, Holthaus, Sophia-Martha kleine, additional, Azam, Selina A., additional, Duran, Yanai, additional, Ribeiro, Joana, additional, Luhmann, Ulrich F. O., additional, Bainbridge, James W. B., additional, Smith, Alexander J., additional, and Ali, Robin R., additional

Published
2015
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164. A prospective longitudinal study of retinal structure and function in achromatopsia.

Author

Aboshiha, Jonathan, Aboshiha, Jonathan, Dubis, Adam M, Cowing, Jill, Fahy, Rachel TA, Sundaram, Venki, Bainbridge, James W, Ali, Robin R, Dubra, Alfredo, Nardini, Marko, Webster, Andrew R, Moore, Anthony T, Rubin, Gary, Carroll, Joseph, Michaelides, Michel, Aboshiha, Jonathan, Aboshiha, Jonathan, Dubis, Adam M, Cowing, Jill, Fahy, Rachel TA, Sundaram, Venki, Bainbridge, James W, Ali, Robin R, Dubra, Alfredo, Nardini, Marko, Webster, Andrew R, Moore, Anthony T, Rubin, Gary, Carroll, Joseph, and Michaelides, Michel

Abstract

PurposeTo longitudinally characterize retinal structure and function in achromatopsia (ACHM) in preparation for clinical gene therapy trials.MethodsThirty-eight molecularly confirmed ACHM subjects underwent serial assessments, including spectral domain optical coherence tomography (SD-OCT), microperimetry, and fundus autofluorescence (FAF). Foveal structure on SD-OCT was graded and compared for evidence of progression, along with serial measurements of foveal total retinal thickness (FTRT) and outer nuclear layer (ONL) thickness. Fundus autofluorescence patterns were characterized and compared over time.ResultsMean follow-up was 19.5 months (age range at baseline, 6-52 years). Only 2 (5%) of 37 subjects demonstrated change in serial foveal SD-OCT scans. There was no statistically significant change over time in FTRT (P = 0.83), ONL thickness (P = 0.27), hyporeflective zone diameter (P = 0.42), visual acuity (P = 0.89), contrast sensitivity (P = 0.22), mean retinal sensitivity (P = 0.84), and fixation stability (P = 0.58). Three distinct FAF patterns were observed (n = 30): central increased FAF (n = 4), normal FAF (n = 11), and well-demarcated reduced FAF (n = 15); with the latter group displaying a slow increase in the area of reduced FAF of 0.03 mm(2) over 19.3 months (P = 0.002).ConclusionsPreviously published cross-sectional studies have described conflicting findings with respect to the age-dependency of progression. This study, which constitutes the largest and longest prospective longitudinal study of ACHM to date, suggests that although ACHM may be progressive, any such progression is slow and subtle in most patients, and does not correlate with age or genotype. We also describe the first serial assessment of FAF, which is highly variable between individuals, even of similar age and genotype.

Published
2014

165. Hsp90 inhibition protects against inherited retinal degeneration

Author

Universitat Politècnica de Catalunya. Departament d'Enginyeria Química, Universitat Politècnica de Catalunya. GBMI - Grup de Biotecnologia Molecular i Industrial, Aguilà, Mònica, Bevilacqua, Dalila, McCulley, Caroline, Schwarz, Nele, Athanasiou, Dimitra, Kanuga, Naheed, Novoselov, Sergey S., Lange, Clemens A.K., Ali, Robin R., Bainbridge, James W., Gias, Carlos, Coffey, Peter J., Garriga Solé, Pere, Cheetham, Michael E., Universitat Politècnica de Catalunya. Departament d'Enginyeria Química, Universitat Politècnica de Catalunya. GBMI - Grup de Biotecnologia Molecular i Industrial, Aguilà, Mònica, Bevilacqua, Dalila, McCulley, Caroline, Schwarz, Nele, Athanasiou, Dimitra, Kanuga, Naheed, Novoselov, Sergey S., Lange, Clemens A.K., Ali, Robin R., Bainbridge, James W., Gias, Carlos, Coffey, Peter J., Garriga Solé, Pere, and Cheetham, Michael E.

Abstract

The molecular chaperone Hsp90 is important for the functional maturation of many client proteins, and inhibitors are in clinical trials for multiple indications in cancer. Hsp90 inhibition activates the heat shock response and can improve viability in a cell model of the P23H misfolding mutation in rhodopsin that causes autosomal dominant retinitis pigmentosa (adRP). Here, we show that a single low dose of the Hsp90 inhibitor HSP990 enhanced visual function and delayed photoreceptor degeneration in a P23H transgenic rat model. This was associated with the induction of heat shock protein expression and reduced rhodopsin aggregation. We then investigated the effect of Hsp90 inhibition on a different type of rod opsin mutant, R135L, which is hyperphosphorylated, binds arrestin and disrupts vesicular traffic. Hsp90 inhibition with 17-AAG reduced the intracellular accumulation of R135L and abolished arrestin binding in cells. Hsf-1(/) cells revealed that the effect of 17-AAG on P23H aggregation was dependent on HSF-1, whereas the effect on R135L was HSF-1 independent. Instead, the effect on R135L was mediated by a requirement of Hsp90 for rhodopsin kinase (GRK1) maturation and function. Importantly, Hsp90 inhibition restored R135L rod opsin localization to wild-type (WT) phenotype in vivo in rat retina. Prolonged Hsp90 inhibition with HSP990 in vivo led to a posttranslational reduction in GRK1 and phosphodiesterase (PDE6) protein levels, identifying them as Hsp90 clients. These data suggest that Hsp90 represents a potential therapeutic target for different types of rhodopsin adRP through distinct mechanisms, but also indicate that sustained Hsp90 inhibition might adversely affect visual function., Peer Reviewed, Postprint (published version)

Published
2014

167. The severity of retinal pathology in homozygous Crb1rd8/rd8 mice is dependent on additional genetic factors

Author

Luhmann, Ulrich F.O., primary, Carvalho, Livia S., additional, Holthaus, Sophia-Martha kleine, additional, Cowing, Jill A., additional, Greenaway, Simon, additional, Chu, Colin J., additional, Herrmann, Philipp, additional, Smith, Alexander J., additional, Munro, Peter M.G., additional, Potter, Paul, additional, Bainbridge, James W.B., additional, and Ali, Robin R., additional

Published
2014
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169. Prevention of Photoreceptor Cell Loss in a Cln6nclfMouse Model of Batten Disease Requires CLN6Gene Transfer to Bipolar Cells

Author

kleine Holthaus, Sophia-Martha, Ribeiro, Joana, Abelleira-Hervas, Laura, Pearson, Rachael A., Duran, Yanai, Georgiadis, Anastasios, Sampson, Robert D., Rizzi, Matteo, Hoke, Justin, Maswood, Ryea, Azam, Selina, Luhmann, Ulrich F.O., Smith, Alexander J., Mole, Sara E., and Ali, Robin R.

Abstract

The neuronal ceroid lipofuscinoses (NCLs) are inherited lysosomal storage disorders characterized by general neurodegeneration and premature death. Sight loss is also a major symptom in NCLs, severely affecting the quality of life of patients, but it is not targeted effectively by brain-directed therapies. Here we set out to explore the therapeutic potential of an ocular gene therapy to treat sight loss in NCL due to a deficiency in the transmembrane protein CLN6. We found that, although Cln6nclfmice presented mainly with photoreceptor degeneration, supplementation of CLN6 in photoreceptors was not beneficial. Because the level of CLN6is low in photoreceptors but high in bipolar cells (retinal interneurons that are only lost in Cln6-deficient mice at late disease stages), we explored the therapeutic effects of delivering CLN6to bipolar cells using adeno-associated virus (AAV) serotype 7m8. Bipolar cell-specific expression of CLN6slowed significantly the loss of photoreceptor function and photoreceptor cells. This study shows that the deficiency of a gene normally expressed in bipolar cells can cause the loss of photoreceptors and that this can be prevented by bipolar cell-directed treatment.

Published
2018
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171. Hsp90 inhibition protects against inherited retinal degeneration

Author

Aguilà, Mònica, primary, Bevilacqua, Dalila, additional, McCulley, Caroline, additional, Schwarz, Nele, additional, Athanasiou, Dimitra, additional, Kanuga, Naheed, additional, Novoselov, Sergey S., additional, Lange, Clemens A.K., additional, Ali, Robin R., additional, Bainbridge, James W., additional, Gias, Carlos, additional, Coffey, Peter J., additional, Garriga, Pere, additional, and Cheetham, Michael E., additional

Published
2013
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172. Evaluating soil contamination risks by using MicroLEIS DSS in El-Fayoum Nile province, Egypt.

Author

Abd-Elmabod, S.K., Ali, Robin R., Anaya Romero, María, Rosa, Diego de la, Abd-Elmabod, S.K., Ali, Robin R., Anaya Romero, María, and Rosa, Diego de la

Abstract

The Agro-ecological Decision Support System, MicroLEIS DSS, was applied to investigate and predict soil degradation in the province of El-Fayoum, one of the western desert areas of the Arab Republic of Egypt, with an area of 149,300 ha approximately.

Published
2010

173. Effect of Gene Therapy on Visual Function in Leber's Congenital Amaurosis

Author

British Retinitis Pigmentosa Society, Department of Health & Social Care (UK), Wellcome Trust, Medical Research Council (UK), Foundation Fighting Blindness, University College London, Bainbridge, James W. B., Smith, Alexander J., Barker, Susie S., Robbie, Scott, Henderson, Robert H., Balaggan, Kamaljit, Viswanathan, Ananth, Holder, Graham E., Stockman, Andrew, Tyler, Nick, Petersen-Jones, Simon, Bhattacharya, Shom Shanker, Thrasher, Adrián J., Fitzke, Fred W., Carter, Barrie J., Rubin, Gary S., Moore, Anthony T., Ali, Robin R., British Retinitis Pigmentosa Society, Department of Health & Social Care (UK), Wellcome Trust, Medical Research Council (UK), Foundation Fighting Blindness, University College London, Bainbridge, James W. B., Smith, Alexander J., Barker, Susie S., Robbie, Scott, Henderson, Robert H., Balaggan, Kamaljit, Viswanathan, Ananth, Holder, Graham E., Stockman, Andrew, Tyler, Nick, Petersen-Jones, Simon, Bhattacharya, Shom Shanker, Thrasher, Adrián J., Fitzke, Fred W., Carter, Barrie J., Rubin, Gary S., Moore, Anthony T., and Ali, Robin R.

Abstract

Early-onset, severe retinal dystrophy caused by mutations in the gene encoding retinal pigment epithelium–specific 65-kD protein (RPE65) is associated with poor vision at birth and complete loss of vision in early adulthood. We administered to three young adult patients subretinal injections of recombinant adeno-associated virus vector 2/2 expressing RPE65 complementary DNA (cDNA) under the control of a human RPE65 promoter. There were no serious adverse events. There was no clinically significant change in visual acuity or in peripheral visual fields on Goldmann perimetry in any of the three patients. We detected no change in retinal responses on electroretinography. One patient had significant improvement in visual function on microperimetry and on dark-adapted perimetry. This patient also showed improvement in a subjective test of visual mobility. These findings provide support for further clinical studies of this experimental approach in other patients with mutant RPE65. (ClinicalTrials.gov number, NCT00643747.)

Published
2008

175. Successful Gene Therapy in Older Rpe65-Deficient Dogs Following Subretinal Injection of an Adeno-Associated Vector Expressing RPE65

Author

Annear, Matthew J., primary, Mowat, Freya M., additional, Bartoe, Joshua T., additional, Querubin, Janice, additional, Azam, Selina A., additional, Basche, Mark, additional, Curran, Paul G., additional, Smith, Alexander J., additional, Bainbridge, James W.B., additional, Ali, Robin R., additional, and Petersen-Jones, Simon M., additional

Published
2013
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176. Photoreceptor precursors derived from three-dimensional embryonic stem cell cultures integrate and mature within adult degenerate retina

Author

Gonzalez-Cordero, Anai, primary, West, Emma L, additional, Pearson, Rachael A, additional, Duran, Yanai, additional, Carvalho, Livia S, additional, Chu, Colin J, additional, Naeem, Arifa, additional, Blackford, Samuel J I, additional, Georgiadis, Anastasios, additional, Lakowski, Jorn, additional, Hubank, Mike, additional, Smith, Alexander J, additional, Bainbridge, James W B, additional, Sowden, Jane C, additional, and Ali, Robin R, additional

Published
2013
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179. Repair of the degenerate retina by photoreceptor transplantation

Author

Barber, Amanda C., primary, Hippert, Claire, additional, Duran, Yanai, additional, West, Emma L., additional, Bainbridge, James W. B., additional, Warre-Cornish, Katherine, additional, Luhmann, Ulrich F. O., additional, Lakowski, Jorn, additional, Sowden, Jane C., additional, Ali, Robin R., additional, and Pearson, Rachael A., additional

Published
2012
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180. The Relevance of Chemokine Signalling in Modulating Inherited and Age-Related Retinal Degenerations.

Author

Luhmann, Ulrich FO, Robbie, Scott J, Bainbridge, James WB, and Ali, Robin R

Abstract

Systemic monocytes, tissue resident macrophages, dendritic cells and microglia have specific roles in immune surveillance and maintenance of tissue homeostasis and are key regulator and effector cells of the local immune response to acute and chronic tissue injury. Two major signalling pathways that differentially define trafficking behaviour and activation of systemic and local myeloid cell populations in response to exogenous and endogenous inflammatory stimuli are the Ccl2-Ccr2 and the Cx3cl1-Cx3cr1 chemokine pathways. Alterations in these pathways have been implicated in controlling myeloid cell activation during normal ageing and in age-related retinal degenerations, including age-related macular degeneration (AMD). We review the evidence for how altered chemokine signalling in acute and chronic inflammatory conditions regulate local and systemic myeloid cell responses in the retina and how this may contribute to or attenuate pathology in inherited and age-related retinal diseases. We discuss the role of environmental factors (e.g. light exposure) and the influence of genetic factors on the manifestation of pathology in experimental models and in human patients and how we envisage harnessing this knowledge for the development of targeted, more broadly applicable anti-inflammatory treatment strategies for a wide range of retinal degenerations. [ABSTRACT FROM AUTHOR]

Published
2014
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182. Von Hippel-Lindau protein in the RPE is essential for normal ocular growth and vascular development

Author

Lange, Clemens A. K., primary, Luhmann, Ulrich F. O., additional, Mowat, Freya M., additional, Georgiadis, Anastasios, additional, West, Emma L., additional, Abrahams, Sabu, additional, Sayed, Haroon, additional, Powner, Michael B., additional, Fruttiger, Marcus, additional, Smith, Alexander J., additional, Sowden, Jane C., additional, Maxwell, Patrick H., additional, Ali, Robin R., additional, and Bainbridge, James W. B., additional

Published
2012
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184. Differential Modulation of Retinal Degeneration by Ccl2 and Cx3cr1 Chemokine Signalling

Author

Luhmann, Ulrich F. O., primary, Lange, Clemens A., additional, Robbie, Scott, additional, Munro, Peter M. G., additional, Cowing, Jill A., additional, Armer, Hannah E. J., additional, Luong, Vy, additional, Carvalho, Livia S., additional, MacLaren, Robert E., additional, Fitzke, Frederick W., additional, Bainbridge, James W. B., additional, and Ali, Robin R., additional

Published
2012
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187. Leber Congenital Amaurosis Associated with AIPL1: Challenges in Ascribing Disease Causation, Clinical Findings, and Implications for Gene Therapy

Author

Tan, Mei Hong, primary, Mackay, Donna S., additional, Cowing, Jill, additional, Tran, Hoai Viet, additional, Smith, Alexander J., additional, Wright, Genevieve A., additional, Dev-Borman, Arundhati, additional, Henderson, Robert H., additional, Moradi, Phillip, additional, Russell-Eggitt, Isabelle, additional, MacLaren, Robert E., additional, Robson, Anthony G., additional, Cheetham, Michael E., additional, Thompson, Dorothy A., additional, Webster, Andrew R., additional, Michaelides, Michel, additional, Ali, Robin R., additional, and Moore, Anthony T., additional

Published
2012
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190. Educational paper

Author

Sundaram, Venki, primary, Moore, Anthony T., additional, Ali, Robin R., additional, and Bainbridge, James W., additional

Published
2011
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194. Lentiviral Vector Integration Profiles Differ in Rodent Postmitotic Tissues

Author

Bartholomae, Cynthia C, primary, Arens, Anne, additional, Balaggan, Kamaljit S, additional, Yáñez-Muñoz, Rafael J, additional, Montini, Eugenio, additional, Howe, Steven J, additional, Paruzynski, Anna, additional, Korn, Bernhard, additional, Appelt, Jens Uwe, additional, MacNeil, Angus, additional, Cesana, Daniela, additional, Abel, Ulrich, additional, Glimm, Hanno, additional, Naldini, Luigi, additional, Ali, Robin R, additional, Thrasher, Adrian J, additional, von Kalle, Christof, additional, and Schmidt, Manfred, additional

Published
2011
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197. The Tight Junction Associated Signalling Proteins ZO-1 and ZONAB Regulate Retinal Pigment Epithelium Homeostasis in Mice

Author

Georgiadis, Anastasios, primary, Tschernutter, Marion, additional, Bainbridge, James W. B., additional, Balaggan, Kamaljit S., additional, Mowat, Freya, additional, West, Emma L., additional, Munro, Peter M. G., additional, Thrasher, Adrian J., additional, Matter, Karl, additional, Balda, Maria S., additional, and Ali, Robin R., additional

Published
2010
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199. GFAP-Driven GFP Expression in Activated Mouse Müller Glial Cells Aligning Retinal Blood Vessels Following Intravitreal Injection of AAV2/6 Vectors

Author

Aartsen, Wendy M., primary, van Cleef, Koen W. R., additional, Pellissier, Lucie P., additional, Hoek, Robert M., additional, Vos, Rogier M., additional, Blits, Bas, additional, Ehlert, Erich M. E., additional, Balaggan, Kamaljit S., additional, Ali, Robin R., additional, Verhaagen, Joost, additional, and Wijnholds, Jan, additional

Published
2010
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