Characterization of a dehydrogenase activity responsible for oxidation of 11-cis-retinol in the retinal pigment epithelium of mice with a disrupted RDH5 gene. A model for the human hereditary disease fundus albipunctatus.
Publication year
2001Source
Journal of Biological Chemistry, 276, 35, (2001), pp. 3245-65ISSN
Publication type
Article / Letter to editor

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Organization
Ophthalmology
Journal title
Journal of Biological Chemistry
Volume
vol. 276
Issue
iss. 35
Page start
p. 3245
Page end
p. 65
Subject
Hereditary and acquired vitreo-retinal disorders: experimental and clinical research and treatment.; Erfelijke en verworven vitreo-retinale aandoeningen: experimenteel en klinisch onderzoek en behandeling.Abstract
In the vertebrate retina, the final step of visual chromophore production is the oxidation of 11-cis-retinol to 11-cis-retinal. This reaction is catalyzed by 11-cis-retinol dehydrogenases (11-cis-RDHs), prior to the chromophore rejoining with the visual pigment apo-proteins. The RDH5 gene encodes a dehydrogenase that is responsible for the majority of RDH activity. In humans, mutations in this gene are associated with fundus albipunctatus, a disease expressed by delayed dark adaptation of both cones and rods. In this report, an animal model for this disease, 11-cis-rdh-/- mice, was used to investigate the flow of retinoids after a bleach, and microsomal membranes from the retinal pigment epithelium of these mice were employed to characterize remaining enzymatic activities oxidizing 11-cis-retinol. Lack of 11-cis-RDH leads to an accumulation of cis-retinoids, particularly 13-cis-isomers. The analysis of 11-cis-rdh-/- mice showed that the RDH(s) responsible for the production of 11-cis-retinal displays NADP-dependent specificity toward 9-cis- and 11-cis-retinal but not 13-cis-retinal. The lack of 13-cis-RDH activity could be a reason why 13-cis-isomers accumulate in the retinal pigment epithelium of 11-cis-rdh-/- mice. Furthermore, our results provide detailed characterization of a mouse model for the human disease fundus albipunctatus and emphasize the importance of 11-cis-RDH in keeping the balance between different components of the retinoid cycle.
This item appears in the following Collection(s)
- Academic publications [202802]
- Electronic publications [100870]
- Faculty of Medical Sciences [80020]
- Open Access publications [69592]
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