Towards optogenetic vision restoration with high resolution

by Ulisse Ferrari, St éphane Deny, Abhishek Sengupta, Romain Caplette, Francesco Trapani, José-Alain Sahel, Deniz Dalkara, Serge Picaud, Jens Duebel, Olivier Marre In many cases of inherited retinal degenerations, ganglion cells are spared despite photoreceptor cell death, making it possible to stimulate them to restore visual function. Several studies have shown that it is possible to express an optogenetic protein in ganglion cells and make them light sens itive, a promising strategy to restore vision. However the spatial resolution of optogenetically-reactivated retinas has rarely been measured, especially in the primate. 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 ther apy. We show that optogenetically 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 gang lion cells would respond to letters of different sizes. We then estimated the maximal acuity expected by a patient, assuming it coul...
Source: PLoS Computational Biology - Category: Biology Authors: Source Type: research