Optogenetic therapy: high spatiotemporal resolution and pattern discrimination compatible with vision restoration in non-human primates

• Published in: Communications biology Vol. 4; no. 1; p. 125
• Main Authors: Gauvain, Gregory, Akolkar, Himanshu, Chaffiol, Antoine, Arcizet, Fabrice, Khoei, Mina A., Desrosiers, Mélissa, Jaillard, Céline, Caplette, Romain, Marre, Olivier, Bertin, Stéphane, Fovet, Claire-Maelle, Demilly, Joanna, Forster, Valérie, Brazhnikova, Elena, Hantraye, Philippe, Pouget, Pierre, Douar, Anne, Pruneau, Didier, Chavas, Joël, Sahel, José-Alain, Dalkara, Deniz, Duebel, Jens, Benosman, Ryad, Picaud, Serge
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.01.2021; Nature Publishing Group; Nature Portfolio
• Subjects: 14/19; 14/35; 14/69; 631/378/2613/1786; 692/308/575; 9/74; 96/44; Acuity; Age; Biology; Biomedical and Life Sciences; Blindness; Clinical trials; DNA nucleotidylexotransferase; Genetics; Information processing; Life Sciences; Macular degeneration; Optics; Patients; Photons; Retina; Retinal degeneration; Retinal ganglion cells; Retinitis; Retinitis pigmentosa; Transfection; Vision; Visual discrimination
• ISSN: 2399-3642; 2399-3642
• DOI: 10.1038/s42003-020-01594-w

Vision restoration is an ideal medical application for optogenetics, because the eye provides direct optical access to the retina for stimulation. Optogenetic therapy could be used for diseases involving photoreceptor degeneration, such as retinitis pigmentosa or age-related macular degeneration. We describe here the selection, in non-human primates, of a specific optogenetic construct currently tested in a clinical trial. We used the microbial opsin ChrimsonR, and showed that the AAV2.7m8 vector had a higher transfection efficiency than AAV2 in retinal ganglion cells (RGCs) and that ChrimsonR fused to tdTomato (ChR-tdT) was expressed more efficiently than ChrimsonR. Light at 600 nm activated RGCs transfected with AAV2.7m8 ChR-tdT, from an irradiance of 10 15 photons.cm −2 .s −1 . Vector doses of 5 × 10 10 and 5 × 10 11 vg/eye transfected up to 7000 RGCs/mm 2 in the perifovea, with no significant immune reaction. We recorded RGC responses from a stimulus duration of 1 ms upwards. When using the recorded activity to decode stimulus information, we obtained an estimated visual acuity of 20/249, above the level of legal blindness (20/400). These results lay the groundwork for the ongoing clinical trial with the AAV2.7m8 - ChR-tdT vector for vision restoration in patients with retinitis pigmentosa. Gauvain et al demonstrate that optogenetic therapy using the AAV2.7m8- ChR-tdT construct can partially restore vision in non-human primates to levels above those considered legally-blind. This study enables the identification of the most suitable construct for ongoing clinical trials attempting vision restoration in patients with retinitis pigmentosa.