The expression of light-sensitive microbial opsins is a promising mutation-independent approach to restore vision in retinal degenerative diseases. Using viral vectors, optogenetic tools can be genetically expressed in various subpopulations of retinal neurons. The choice of cell type depends on the availability of surviving retinal cells. If cones are still alive but they lack outer segments, they can be targeted with optogenetic inhibitors, such as halorhodopsin. Alternatively, it is possible to bypass the photoreceptors and to target bipolar cells. In late-stage degeneration, when bipolar cells degenerate, "artificial photoreceptors" can be made from retinal ganglion cells, but with this approach, upstream retinal processing cannot be utilized. However, when ganglion cells are stimulated directly, higher brain regions might be able to compensate for some loss of retinal processing, which is indicated by clinical studies with epiretinal implants, where patients can perform simple visual tasks. Finally, optogenetics in combination with neuroprotective approaches could serve as a valuable strategy to restore the function of remaining cells, as well as to rescue retinal neurons from progressive degeneration.
Keywords: Channelrhodopsin; Opsins; Optogenetics; Retina; Retinal disease; Vision restoration.