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

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