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Optogenetics for visual restoration: From proof of principle to translational challenges

Lindner, M; Gilhooley, MJ; Hughes, S; Hankins, MW; (2022) Optogenetics for visual restoration: From proof of principle to translational challenges. Progress in Retinal and Eye Research , Article 101089. 10.1016/j.preteyeres.2022.101089. (In press). Green open access

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Abstract

Degenerative retinal disorders are a diverse family of diseases commonly leading to irreversible photoreceptor death, while leaving the inner retina relatively intact. Over recent years, innovative gene replacement therapies aiming to halt the progression of certain inherited retinal disorders have made their way into clinics. By rendering surviving retinal neurons light sensitive optogenetic gene therapy now offers a feasible treatment option that can restore lost vision, even in late disease stages and widely independent of the underlying cause of degeneration. Since proof-of-concept almost fifteen years ago, this field has rapidly evolved and a detailed first report on a treated patient has recently been published. In this article, we provide a review of optogenetic approaches for vision restoration. We discuss the currently available optogenetic tools and their relative advantages and disadvantages. Possible cellular targets will be discussed and we will address the question how retinal remodelling may affect the choice of the target and to what extent it may limit the outcomes of optogenetic vision restoration. Finally, we will analyse the evidence for and against optogenetic tool mediated toxicity and will discuss the challenges associated with clinical translation of this promising therapeutic concept.

Type: Article
Title: Optogenetics for visual restoration: From proof of principle to translational challenges
Location: England
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.preteyeres.2022.101089
Publisher version: https://doi.org/10.1016/j.preteyeres.2022.101089
Language: English
Additional information: © 2022 Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: Channelrhodopsin, Gene therapy, Melanopsin, Optogenetics, Remodelling, Retina
UCL classification: UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > Institute of Ophthalmology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL
URI: https://discovery.ucl.ac.uk/id/eprint/10153361
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