Inherited retinal degenerations such as retinitis pigmentosa (RP) affect approximately 1 in 3000 people and are the leading cause of blindness in working age adults in England and Wales. In these, typically monogenic, conditions there is progressive degeneration of photoreceptors, however inner retinal neurons such as bipolar cells and ganglion cells remain largely structurally intact, even in end-stage disease. Optogenetics is a method of neuromodulation that has wide applicability in neuroscience, and utilises light to activate neurons that have been engineered to ectopically express a light-sensitive protein. Given this naturally occurs in the eye when light triggers phototransduction in rods and cones, an intuitive application of optogenetic techniques would be to induce light sensitivity in remaining retinal cells and restore vision in end-stage retinal degenerations.  Developing an effective optogenetic approach requires consideration of multiple factors including the light-sensitive protein that is used, the method of gene delivery and the target cell for expression.  A range of photosensitive proteins have been investigated including microbial opsins e.g. channelrhodopsin and halorhodopsin; mammalian opsins e.g. rhodopsin, cone opsin and melanopsin, and engineered ion channels. These vary in sensitivity, kinetics of their response and wavelength of light causing peak stimulation. Gene therapy using adeno-associated viral vectors (AAV) has been extensively investigated for gene transfer to the retina, with the first gene therapy now licensed for the treatment of a rare retinal disorder. Modification of surface amino acid residues on AAV vectors, the promoter driving gene expression and administration via subretinal or intravitreal injection, all impact vector efficacy and which retinal cell type expresses the light sensitive protein. This in turn influences potential visual output: for example transducing bipolar cells, the most distal remaining neuron in visual circuitry in end-stage RP, may preserve processing of signals within the retina, but thus far these cells have proven most difficult to target. In this talk, we will explore different optogenetic approaches with a focus on human melanopsin gene therapy (De Silva et al, 2017*), and the current clinical trials now underway to evaluate optogenetic gene therapy in reversing visual loss in end-stage retinitis pigmentosa.