title: Conditional Ablation of Retinol Dehydrogenase 10 in the Retinal Pigmented Epithelium Causes Delayed Dark Adaption in Mice.
abstract: Regeneration of the visual chromophore, 11-cis-retinal, is a crucial step in the visual cycle required to sustain vision. This cycle consists of sequential biochemical reactions that occur in photoreceptor cells and the retinal pigmented epithelium (RPE). Oxidation of 11-cis-retinol to 11-cis-retinal is accomplished by a family of enzymes termed 11-cis-retinol dehydrogenases, including RDH5 and RDH11. Double deletion of Rdh5 and Rdh11 does not limit the production of 11-cis-retinal in mice. Here we describe a third retinol dehydrogenase in the RPE, RDH10, which can produce 11-cis-retinal. Mice with a conditional knock-out of Rdh10 in RPE cells (Rdh10 cKO) displayed delayed 11-cis-retinal regeneration and dark adaption after bright light illumination. Retinal function measured by electroretinogram after light exposure was also delayed in Rdh10 cKO mice as compared with controls. Double deletion of Rdh5 and Rdh10 (cDKO) in mice caused elevated 11/13-cis-retinyl ester content also seen in Rdh5(-/-)Rdh11(-/-) mice as compared with Rdh5(-/-) mice. Normal retinal morphology was observed in 6-month-old Rdh10 cKO and cDKO mice, suggesting that loss of Rdh10 in the RPE does not negatively affect the health of the retina. Compensatory expression of other retinol dehydrogenases was observed in both Rdh5(-/-) and Rdh10 cKO mice. These results indicate that RDH10 acts in cooperation with other RDH isoforms to produce the 11-cis-retinal chromophore needed for vision.
authors.affiliation: Departments of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106.
authors.forename: Bhubanananda
authors.initials: B
authors.lastname: Sahu
authors.affiliation: Polgenix, Inc., Cleveland, Ohio 44106.
authors.forename: Wenyu
authors.initials: W
authors.lastname: Sun
authors.affiliation: Departments of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106.
authors.forename: Lindsay
authors.initials: L
authors.lastname: Perusek
authors.affiliation: Departments of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106.
authors.forename: Vipulkumar
authors.initials: V
authors.lastname: Parmar
authors.affiliation: Departments of Medicine Endocrinology, Cell Biology, and Ophthalmology and the Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104.
authors.forename: Yun-Zheng
authors.initials: YZ
authors.lastname: Le
authors.affiliation: School of Molecular Biosciences, Washington State University, Pullman, Washington 99164.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Griswold
authors.affiliation: Departments of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106; Cleveland Center for Membrane and Structural Biology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106.
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Palczewski
authors.affiliation: Departments of Ophthalmology and Visual Sciences, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106; Departments of Pharmacology, Case Western Reserve University, School of Medicine, Cleveland, Ohio 44106. Electronic address: aam19@case.edu.
authors.forename: Akiko
authors.initials: A
authors.lastname: Maeda
mesh_terms: D000429:Alcohol Oxidoreductases / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003623:Dark Adaptation / Q000502:physiology*; D005260:Female; D015870:Gene Expression; D007700:Kinetics; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010088:Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012162:Retinal Degeneration / Q000201:enzymology / Q000209:etiology; D055213:Retinal Pigment Epithelium / Q000033:anatomy & histology / Q000201:enzymology* / Q000502:physiology; D012172:Retinaldehyde / Q000096:biosynthesis; D012176:Retinoids / Q000378:metabolism; D061987:Sf9 Cells; D018411:Spodoptera
chemical_list: D012333:RNA, Messenger; D011994:Recombinant Proteins; D012176:Retinoids; D010088:Oxidoreductases; C486028:Rdh11 protein, mouse; D000429:Alcohol Oxidoreductases; C113992:trans-retinol dehydrogenase; C105846:retinol dehydrogenase 5; D012172:Retinaldehyde
keywords: RDH10; RDH11; RDH5; dark adaption; dehydrogenase; retina; retinal degeneration; retinal pigmented epithelium; retinoid; retinol; retinol dehydrogenase; vision