Abstract
To date, clinical gene therapy efforts for inherited retinal degeneration (IRD) have focused largely on gene replacement. The large number of genes and alleles causing IRD, however, makes this approach practical only for the most common causes. Additionally, gene replacement therapy cannot reverse existing retinal degeneration. Viral-mediated gene therapy can be used for two other approaches to slow or reverse IRD. First, by driving intraocular expression of growth factors or neuroprotective proteins, retinal degeneration can be slowed. Second, by expressing light-sensitive proteins (either microbial channelopsins or mammalian G-protein coupled opsins) in preserved inner retinal neurons, light sensitivity can be restored to the blind retina. Both approaches have advanced substantially in the past decade, and both are nearing clinical tests. This review surveys recent progress in these approaches.