{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T04:10:42Z","timestamp":1790741442893,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T00:00:00Z","timestamp":1660694400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["094448\/Z\/10\/Z"],"award-info":[{"award-number":["094448\/Z\/10\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100002089","name":"Fight for Sight","doi-asserted-by":"publisher","award":["5099\/5100"],"award-info":[{"award-number":["5099\/5100"]}],"id":[{"id":"10.13039\/100002089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Inherited retinal degenerations such as retinitis pigmentosa (RP) affect around one in 4000 people and are the leading cause of blindness in working age adults in several countries. In these typically monogenic conditions, there is progressive degeneration of photoreceptors; however, inner retinal neurons such as bipolar cells and ganglion cells remain largely structurally intact, even in end\u2010stage disease. Therapeutic approaches aiming to stimulate these residual cells, independent of the underlying genetic cause, could potentially restore visual function in patients with advanced vision loss, and benefit many more patients than therapies directed at the specific gene implicated in each disorder. One approach investigated for this purpose is that of optogenetics, a method of neuromodulation that utilises light to activate neurons engineered to ectopically express a light\u2010sensitive protein. Using gene therapy via adeno\u2010associated viral vectors, a range of photosensitive proteins have been expressed in remaining retinal cells in advanced retinal degeneration with <jats:italic>in vivo<\/jats:italic> studies demonstrating restoration of visual function. Developing an effective optogenetic strategy requires consideration of multiple factors, including the light\u2010sensitive protein that is used, the vector and method for gene delivery, and the target cell for expression because these in turn may affect the quality of vision that can be restored. Currently, at least four clinical trials are ongoing to investigate optogenetic therapies in patients, with the ultimate aim of reversing visual loss in end\u2010stage disease.\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp15213-gra-0001-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text><\/jats:p>","DOI":"10.1113\/jp282076","type":"journal-article","created":{"date-parts":[[2022,7,31]],"date-time":"2022-07-31T15:39:42Z","timestamp":1659281982000},"page":"4623-4632","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Optogenetic approaches to therapy for inherited retinal degenerations"],"prefix":"10.1113","volume":"600","author":[{"given":"Samantha R.","family":"De Silva","sequence":"first","affiliation":[{"name":"Oxford Eye Hospital  Oxford UK"},{"name":"UCL Institute of Ophthalmology  London UK"},{"name":"Nuffield Department of Clinical Neurosciences University of Oxford  Oxford UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony T.","family":"Moore","sequence":"additional","affiliation":[{"name":"UCL Institute of Ophthalmology  London UK"},{"name":"Ophthalmology Department University of California  San Francisco CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01990-7"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09124-x"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2006.02.026"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1177\/2515841418817501"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1190897"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.135112"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.103"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2015.07.029"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08652"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.3752"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.201404077"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.3005708"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1701589114"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/gt.2016.54"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2017.10.004"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature07682"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/mt.2011.69"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.182412299"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1414162111"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/ICU.0000000000000467"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11068-008-9027-6"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preteyeres.2020.100844"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0000299"},{"key":"e_1_2_2_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tins.2007.11.002"},{"key":"e_1_2_2_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(96)79635-2"},{"key":"e_1_2_2_27_1","first-page":"143","article-title":"Morphometric analysis of the extramacular retina from postmortem eyes with retinitis pigmentosa","volume":"40","author":"Humayun M. 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