Optogenetic restoration of retinal ganglion cell activity in the living primate

Optogenetic therapies for vision restoration aim to confer intrinsic light sensitivity to retinal ganglion cells when photoreceptors have degenerated and light sensitivity has been irreversibly lost. We combine adaptive optics ophthalmoscopy with calcium imaging to optically record optogenetically restored retinal ganglion cell activity in the fovea of the living primate. Recording from the intact eye of a living animal, we compare the patterns of activity evoked by the optogenetic actuator ChrimsonR with natural photoreceptor mediated stimulation in the same retinal ganglion cells. Optogenetic responses are recorded more than one year following administration of the therapy and two weeks after acute loss of photoreceptor input in the living animal. This in vivo imaging approach could be paired with any therapy to minimize the number of primates required to evaluate restored activity on the retinal level, while maximizing translational benefit by using an appropriate pre-clinical model of the human visual system. Non-human primate models are important for the development of high quality vision restoration therapies for blindness. Here, the authors demonstrate restoration of light responses in foveal retinal ganglion cells of the living macaque following optogenetic gene therapy.