Melanopsin: Targeted Ectopic Expression for Optogenetic Visual Restoration

Expression of melanopsin renders neural cells sensitive to light, and is emerging as a prime candidate for clinical optogenetic approaches to visual restoration. The retinal neural tissue surviving in the inherited retinal degenerations (IRDs) after visual loss presents a model target for such approaches, however it is unclear if targeting specific neuronal populations within this tissue is advantageous over non-specific delivery. A fair comparison between these two methods is made difficult by the persistence of native photosensitive retinal ganglion cell (pRGC) responses in IRD models. Here we describe a novel model lacking all native retinal light responses to allow a more robust comparison of optogenetic targets. The purpose of our study is to test the hypothesis that retinae devoid of both canonical and pRGC photoreception will remove the "noise" of intrinsic responses and allow comparison of targeted expression of melanopsin in ON-bipolar cells with non-specific delivery.