title: Evidence for RPE65-independent vision in the cone-dominated zebrafish retina.
abstract: An enzyme-based cyclic pathway for trans to cis isomerization of the chromophore of visual pigments (11-cis-retinal) is intrinsic to vertebrate cone and rod vision. This process, called the visual cycle, is mostly characterized in rod-dominated retinas and essentially depends on RPE65, an all-trans to 11-cis-retinoid isomerase. Here we analysed the role of RPE65 in zebrafish, a species with a cone-dominated retina. We cloned zebrafish RPE65 and showed that its expression coincided with photoreceptor development. Targeted gene knockdown of RPE65 resulted in morphologically altered rod outer segments and overall reduced 11-cis-retinal levels. Cone vision of RPE65-deficient larvae remained functional as demonstrated by behavioural tests and by metabolite profiling for retinoids. Furthermore, all-trans retinylamine, a potent inhibitor of the rod visual cycle, reduced 11-cis-retinal levels of control larvae to a similar extent but showed no additive effects in RPE65-deficient larvae. Thus, our study of zebrafish provides in vivo evidence for the existence of an RPE65-independent pathway for the regeneration of 11-cis-retinal for cone vision.
authors.affiliation: University of Zurich, Institute of Zoology, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
authors.forename: Helia B
authors.initials: HB
authors.lastname: Schonthaler
authors.forename: Johanna M
authors.initials: JM
authors.lastname: Lampert
authors.forename: Andrea
authors.initials: A
authors.lastname: Isken
authors.forename: Oliver
authors.initials: O
authors.lastname: Rinner
authors.forename: Andreas
authors.initials: A
authors.lastname: Mader
authors.forename: Matthias
authors.initials: M
authors.lastname: Gesemann
authors.forename: Vitus
authors.initials: V
authors.lastname: Oberhauser
authors.forename: Marcin
authors.initials: M
authors.lastname: Golczak
authors.forename: Oliver
authors.initials: O
authors.lastname: Biehlmaier
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
authors.forename: Stephan C F
authors.initials: SC
authors.lastname: Neuhauss
authors.forename: Johannes
authors.initials: J
authors.lastname: von Lintig
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D002461:Cell Line, Transformed; D004224:Diterpenes / Q000494:pharmacology; D004625:Embryo, Nonmammalian; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D007150:Immunohistochemistry / Q000379:methods; D017403:In Situ Hybridization / Q000379:methods; D008027:Light; D051379:Mice; D012160:Retina / Q000166:cytology* / Q000201:enzymology*; D017949:Retinal Cone Photoreceptor Cells / Q000502:physiology*; D012172:Retinaldehyde / Q000378:metabolism; D014785:Vision, Ocular / Q000502:physiology*; D015027:Zebrafish; D019745:cis-trans-Isomerases / Q000235:genetics / Q000502:physiology*
chemical_list: D004224:Diterpenes; C009167:retinylamine; D019745:cis-trans-Isomerases; D012172:Retinaldehyde