Regeneration of Photopigment Is Enhanced in Mouse Cone Photoreceptors Expressing RPE65 Protein

As cone photoreceptors mediate vision in bright light, their photopigments are bleached at a rapid rate and require substantial recycling of the chromophore 11-cis-retinal (RAL) for continued function. The retinal pigment epithelium (RPE) supplies 11-cis-RAL to both rod and cone photoreceptors; however, stringent demands imposed by the function of cones in bright light exceed the output from this source. Recent evidence has suggested that cones may be able to satisfy this demand through privileged access to an additional source of chromophore located within the inner retina. In this study, we demonstrate that the protein RPE65, previously identified in RPE as the isomerohydrolase of the RPE-retinal visual cycle, is found within cones of the rod-dominant mouse retina, and the level of RPE65 in cones is inversely related to the level in the RPE. The light sensitivity of cone ERGs of BALB/c mice, which had an undetectable level of cone RPE65, was enhanced by approximately threefold with administration of exogenous chromophore, indicating that the cones of these animals are chromophore deficient. This enhancement with chromophore administration was not observed in C57BL/6 mice, whose cones contain RPE65. These results demonstrate that RPE65 within cones may be essential for the efficient regeneration of cone photopigments under bright-light conditions.