Suppressing Retinal Remodeling to Mitigate Vision Loss in Photoreceptor Degenerative Disorders

Abstract

Rod and cone photoreceptors degenerate in retinitis pigmentosa and age-related macular degeneration, robbing the visual system of light-triggered signals necessary for sight. However, changes in the retina do not stop with the photoreceptors. A stereotypical set of morphological and physiological changes, known as remodeling, occur in downstream retinal neurons. Some aspects of remodeling are homeostatic, with structural or functional changes compensating for partial loss of visual inputs. However, other aspects are nonhomeostatic, corrupting retinal information processing to obscure vision mediated naturally by surviving photoreceptors or artificially by vision-restoration technologies. In this review, I consider the mechanism of remodeling and its consequences for residual and restored visual function; discuss the role of retinoic acid, a critical molecular trigger of detrimental remodeling; and discuss strategies for suppressing retinoic acid biosynthesis or signaling as therapeutic possibilities for mitigating vision loss.