Prolonged Inner Retinal Photoreception Depends on the Visual Retinoid Cycle

Abstract

Intrinsically photosensitive retinal ganglion cells (ipRGCs) contain the photopigment melanopsin and drive subconscious physiological responses to light, e.g., pupillary constriction and neuroendocrine regulation. In darkness, each photopigment molecule in ipRGCs, as well as rod/cone photoreceptors, contains 11-cis-retinal (a vitamin A derivative) and light isomerizes it to all-trans-retinal, which activates the photopigment. To make this photopigment excitable again,all-trans-retinal must be reisomerized to 11-cis-retinal. For rods and to some extent cones, this reisomerization occurs in the adjacent retinal pigment epithelium (RPE), but because ipRGCs are far from the RPE, they are thought to regenerate excitable melanopsin exclusively through RPE-independent means. Here, we present electrophysiological and behavioral evidence that ipRGCs depend on the RPE to continuously regenerate melanopsin during intense prolonged photostimulation.