Intra-retinal visual cycle required for rapid and complete cone dark adaptation

Summary Daytime vision is mediated by retinal cones which, unlike rods, remain functional even in bright light and dark-adapt rapidly. These cone properties are enabled by rapid regeneration of their pigment. This in turn requires rapid chromophore recycling which may not be achieved by the canonical retinal pigment epithelium visual cycle. Recent biochemical studies have suggested the presence of a second, cone-specific visual cycle, although its physiological function remains to be established. Here we report that the Müller cells within the salamander neural retina promote cone-specific pigment regeneration and dark adaptation that are independent of the pigment epithelium. Without this pathway, dark adaptation of cones is slow and incomplete. Interestingly, the rates of cone pigment regeneration by the retina and pigment epithelium visual cycles are essentially identical suggesting a possible common rate-limiting step. Finally, we also observed cone dark adaptation in the isolated mouse retina.