title: The retina visual cycle is driven by cis retinol oxidation in the outer segments of cones.
abstract: Vertebrate rod and cone photoreceptors require continuous supply of chromophore for regenerating their visual pigments after photoactivation. Cones, which mediate our daytime vision, demand a particularly rapid supply of 11-cis retinal chromophore in order to maintain their function in bright light. An important contribution to this process is thought to be the chromophore precursor 11-cis retinol, which is supplied to cones from Müller cells in the retina and subsequently oxidized to 11-cis retinal as part of the retina visual cycle. However, the molecular identity of the cis retinol oxidase in cones remains unclear. Here, as a first step in characterizing this enzymatic reaction, we sought to determine the subcellular localization of this activity in salamander red cones. We found that the onset of dark adaptation of isolated salamander red cones was substantially faster when exposing directly their outer vs. their inner segment to 9-cis retinol, an analogue of 11-cis retinol. In contrast, this difference was not observed when treating the outer vs. inner segment with 9-cis retinal, a chromophore analogue which can directly support pigment regeneration. These results suggest, surprisingly, that the cis-retinol oxidation occurs in the outer segments of cone photoreceptors. Confirming this notion, pigment regeneration with exogenously added 9-cis retinol was directly observed in the truncated outer segments of cones, but not in rods. We conclude that the enzymatic machinery required for the oxidation of recycled cis retinol as part of the retina visual cycle is present in the outer segments of cones.
authors.affiliation: Department of Ophthalmology and Visual Sciences,Washington University School of Medicine,Saint Louis,Missouri 63110.
authors.forename: Shinya
authors.initials: S
authors.lastname: Sato
authors.affiliation: Department of Physiology and Biophysics,Boston University School of Medicine,Boston,MA 02118.
authors.forename: Rikard
authors.initials: R
authors.lastname: Frederiksen
authors.affiliation: Department of Physiology and Biophysics,Boston University School of Medicine,Boston,MA 02118.
authors.forename: M Carter
authors.initials: MC
authors.lastname: Cornwall
authors.affiliation: Department of Ophthalmology and Visual Sciences,Washington University School of Medicine,Saint Louis,Missouri 63110.
authors.forename: Vladimir J
authors.initials: VJ
authors.lastname: Kefalov
mesh_terms: D000557:Ambystoma; D000818:Animals; D003623:Dark Adaptation; D004224:Diterpenes; D015591:Microspectrophotometry; D010084:Oxidation-Reduction; D010775:Photic Stimulation; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D055214:Retinal Photoreceptor Cell Outer Segment / Q000502:physiology*; D012168:Retinal Pigments / Q000378:metabolism; D012172:Retinaldehyde / Q000494:pharmacology; D014785:Vision, Ocular / Q000502:physiology*; D014801:Vitamin A / Q000378:metabolism*
chemical_list: D004224:Diterpenes; D012168:Retinal Pigments; D014801:Vitamin A; C031390:9-cis-retinal; D012172:Retinaldehyde
keywords: Cone photoreceptors; Dark adaptation; Pigment regeneration; Retinol dehydrogenase; Visual cycle