Retinol dehydrogenase 8 and ATP‐binding cassette transporter 4 modulate dark adaptation of M‐cones in mammalian retina

摘要

Key points class="unordered" style="list-style-type:disc" id="tjp6845-list-0001">This study explores the molecular mechanisms that regulate the recycling of chromophore required for pigment regeneration in mammalian cones.We report that two chromophore binding proteins, retinol dehydrogenase 8 (RDH8) and photoreceptor‐specific ATP‐binding cassette transporter (ABCA4) accelerate the dark adaptation of cones, first, directly, by facilitating the processing of chromophore in cones, and second, indirectly, by accelerating the turnover of chromophore in rods, which is then recycled and delivered to both rods and cones.Preventing competition with the rods by knocking out rhodopsin accelerated cone dark adaptation, demonstrating the interplay between rod and cone pigment regeneration driven by the retinal pigment epithelium (RPE).This novel interdependence of rod and cone pigment regeneration should be considered when developing therapies targeting the recycling of chromophore for rods, and evaluating residual cone function should be a critical test for such regimens targeting the RPE.