Understanding how photoreceptor degeneration alters retinal signaling, and how to intervene to rescue vision

Age-related Macular Degeneration (AMD) and Retinitis Pigmentosa (RP) are vision disorders caused by loss of rod and cone photoreceptors, but downstream retinal neurons also show physiological and morphological changes, resulting in the emergence of hyperactivity and rhythmic firing in many retinal ganglion cells (RGC). We recently discovered that retinoic acid (RA) is a key signal that triggers hyperactivity and that blockers of RA unmask light responses in RGCs that would otherwise be obscured. Recent work is revealing where in the retina circuit RA initiates functional changes. Moreover, interfering with the RA signaling pathway with drug or gene therapy can improve spatial vision in a mouse model of RP, providing a new strategy for enhancing low vision in human RP and AMD.