A systematic comparison of optogenetic approaches to visual restoration.

Autor:	Gilhooley MJ; Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX1 3QU, UK.; Jules Thorne SCNi, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX1 3QU, UK.; The Institute of Ophthalmology, University College London, 11-43 Bath Street, London EC1V 9EL, UK.; Moorfields Eye Hospital, 162, City Road, London EC1V 2PD, UK., Lindner M; Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX1 3QU, UK.; Jules Thorne SCNi, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX1 3QU, UK.; Institute of Physiology and Pathophysiology, Department of Neurophysiology, Philipps University, Deutschhausstrasse 1-2, Marburg 35037, Germany., Palumaa T; Jules Thorne SCNi, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX1 3QU, UK.; East Tallinn Central Hospital Eye Clinic, Ravi 18, 10138 Tallinn, Estonia., Hughes S; Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX1 3QU, UK.; Jules Thorne SCNi, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX1 3QU, UK., Peirson SN; Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX1 3QU, UK.; Jules Thorne SCNi, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX1 3QU, UK., Hankins MW; Nuffield Laboratory of Ophthalmology, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX1 3QU, UK.; Jules Thorne SCNi, Nuffield Department of Clinical Neuroscience, University of Oxford, Oxford OX1 3QU, UK.
Jazyk:	angličtina
Zdroj:	Molecular therapy. Methods & clinical development [Mol Ther Methods Clin Dev] 2022 Mar 07; Vol. 25, pp. 111-123. Date of Electronic Publication: 2022 Mar 07 (Print Publication: 2022).
DOI:	10.1016/j.omtm.2022.03.003
Abstrakt:	During inherited retinal degenerations (IRDs), vision is lost due to photoreceptor cell death; however, a range of optogenetic tools have been shown to restore light responses in animal models. Restored response characteristics vary between tools and the neuronal cell population to which they are delivered: the interplay between these is complex, but targeting upstream neurons (such as retinal bipolar cells) may provide functional benefit by retaining intraretinal signal processing. In this study, our aim was to compare two optogenetic tools: mammalian melanopsin (hOPN4) and microbial red-shifted channelrhodopsin (ReaChR) expressed within two subpopulations of surviving cells in a degenerate retina. Intravitreal adeno-associated viral vectors and mouse models utilising the Cre/lox system restricted expression to populations dominated by bipolar cells or retinal ganglion cells and was compared with non-targeted delivery using the chicken beta actin (CBA) promoter. In summary, we found bipolar-targeted optogenetic tools produced faster kinetics and flatter intensity-response relationships compared with non-targeted or retinal-ganglion-cell-targeted hOPN4. Hence, optogenetic tools of both mammalian and microbial origins show advantages when targeted to bipolar cells. This demonstrates the advantage of bipolar-cell-targeted optogenetics for vision restoration in IRDs. We therefore developed a bipolar-cell-specific gene delivery system employing a compressed promoter with the potential for clinical translation. Competing Interests: M.L. has received financial support from Heidelberg Engineering, Optos, and Genentech and is an equity owner of Fresenius Medical Care. The other authors declare no competing interests. (© 2022 The Author(s).)
Databáze:	MEDLINE
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