title: Microphthalmia-associated transcription factor regulates the visual cycle genes Rlbp1 and Rdh5 in the retinal pigment epithelium.
abstract: Regeneration of the visual pigment by cells of the retinal pigment epithelium (RPE) is fundamental to vision. Here we show that the microphthalmia-associated transcription factor, MITF, which plays a central role in the development and function of RPE cells, regulates the expression of two visual cycle genes, Rlbp1 which encodes retinaldehyde binding protein-1 (RLBP1), and Rdh5, which encodes retinol dehydrogenase-5 (RDH5). First, we found that Rlbp1 and Rdh5 are downregulated in optic cups and presumptive RPEs of Mitf-deficient mouse embryos. Second, experimental manipulation of MITF levels in human RPE cells in culture leads to corresponding modulations of the endogenous levels of RLBP1 and RDH5. Third, the retinal degeneration associated with the disruption of the visual cycle in Mitf-deficient mice can be partially corrected both structurally and functionally by an exogenous supply of 9-cis-retinal. We conclude that the expression of Rlbp1 and Rdh5 critically depends on functional Mitf in the RPE and suggest that MITF has an important role in controlling retinoid processing in the RPE.
authors.affiliation: Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325003, China.|State Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, 325003, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wen
authors.affiliation: Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325003, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Li
authors.affiliation: Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325003, China.
authors.forename: Huirong
authors.initials: H
authors.lastname: Li
authors.affiliation: Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325003, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325003, China.
authors.forename: Xiaoyin
authors.initials: X
authors.lastname: Ma
authors.affiliation: Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325003, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, 325003, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Lu
authors.affiliation: State Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, 325003, China.
authors.forename: Jia
authors.initials: J
authors.lastname: Qu
authors.affiliation: Laboratory of Developmental Cell Biology and Disease, School of Ophthalmology and Optometry and Eye Hospital, Wenzhou Medical University, Wenzhou, 325003, China.|State Key Laboratory Cultivation Base and Key Laboratory of Vision Science of Ministry of Health and Zhejiang Provincial Key Laboratory of Ophthalmology, Wenzhou Medical University, Wenzhou, 325003, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Hou
mesh_terms: D000429:Alcohol Oxidoreductases / Q000096:biosynthesis* / Q000235:genetics; D000818:Animals; D002352:Carrier Proteins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000172:deficiency / Q000235:genetics*; D012162:Retinal Degeneration / Q000235:genetics* / Q000473:pathology; D055213:Retinal Pigment Epithelium / Q000378:metabolism / Q000473:pathology; D014785:Vision, Ocular / Q000235:genetics* / Q000502:physiology
chemical_list: C020932:11-cis-retinal-binding protein; D002352:Carrier Proteins; D051739:Microphthalmia-Associated Transcription Factor; D000429:Alcohol Oxidoreductases; C105846:retinol dehydrogenase 5