Optogenetic vision restoration with high resolution

Abstract

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.