Biology subjects

Caplette, R.

Publications and source records attributed to Caplette, R..

2 recordsLinked to original sources

bioRxiv2020

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

Restoring vision using optogenetics is an ideal medical application because the eye offers a direct window to access and stimulate the pathological area: the retina. Optogenetic therapy could be applied to diseases with photoreceptor degeneration such as retinitis pigmentosa. Here, we select the specific optogenetic construct that is now used in the clinical trial and assess the opsin functional efficacy on non-human primates retinal ganglion cells (RGCs). We chose the microbial opsin ChrimsonR and showed that the vector AAV2.7m8 produced greater transfection in RGCs compared to AAV2, and that ChrimsonR attached to tdTomato (ChR-tdT) is more efficiently expressed than ChrimsonR. The 600 nm light activates the RGCs transfected with the vector AAV2.7m8-ChR-tdT from an irradiance of 1015 photons.cm-2.s-1. Vector doses of 5.1010 and 5.1011 vg/eye transfect up to 7000 RGCs/mm2 in the perifovea, with no significant immune reaction. Furthermore, using a multielectrode array we recorded RGCs responses starting from 1ms stimulus duration. Using the recorded activity we were able to decode stimulus information and estimate a theoretical visual acuity of 20/249, above legal blindness. Altogether, our results pave the way for the ongoing clinical trial with the AAV2.7m8-ChrimsonR-tdT vector for vision restoration in patients affected by retinitis pigmentosa. One Sentence SummaryWe select here the vector and genetic construct best suited to provide vision restoration in patients suffering from retinopathies, we demonstrate temporal resolution compatible with high dynamic visual scenes and a visual acuity above legal blindness.

neuroscience↗

bioRxiv2018

Optogenetic vision restoration with high resolution

The majority of inherited retinal degenerations are due to photoreceptor cell death. In many cases ganglion cells are spared making it possible to stimulate them to restore visual function. Several studies (Bi et al., 2006; Lin et al., 2008; Sengupta et al., 2016; Caporale et al., 2011; Berry et al., 2017) have shown that it is possible to express an optogenetic protein in ganglion cells and make them light sensitive. This is a promising strategy to restore vision since optical targeting may be more precise than electrical stimulation with a retinal prothesis. However the spatial resolution of optogenetically-reactivated retinas has not been measured with fine-grained stimulation patterns. Since the optogenetic protein is also expressed in axons, it is unclear if these neurons will only be sensitive to the stimulation of a small region covering their somas and dendrites, or if they will also respond to any stimulation overlapping with their axon, dramatically impairing spatial resolution. Here we recorded responses of mouse and macaque retinas to random checkerboard patterns following an in vivo optogenetic therapy. We show that optoge-netically activated ganglion cells are each sensitive to a small region of visual space. A simple model based on this small receptive field predicted accurately their responses to complex stimuli. From this model, we simulated how the entire population of light sensitive ganglion cells would respond to letters of different sizes. We then estimated the maximal acuity expected by a patient, assuming it could make an optimal use of the information delivered by this reactivated retina. The obtained acuity is above the limit of legal blindness. This high spatial resolution is a promising result for future clinical studies.

neuroscience↗