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Rdh12 Activity and Effects on Retinoid Processing in the Murine Retina

Title
Rdh12 Activity and Effects on Retinoid Processing in the Murine Retina
Author
김철영
Keywords
All-trans retinol; Congenital Amaurosis; Lipofuscin; Nrl; RDH12; RPE65; Retinoic Acid; Short Chain Dehydrogenase/Reductase
Issue Date
2009-08
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Citation
JOURNAL OF BIOLOGICAL CHEMISTRY, v. 284, No. 32, Page. 21468-21477
Abstract
RDH12 mutations are responsible for early-onset autosomal recessive retinal dystrophy, which results in profound retinal pathology and severe visual handicap in patients. To investigate the function of RDH12 within the network of retinoid dehydrogenases/reductases (RDHs) present in retina, we studied the retinal phenotype of Rdh12-deficient mice. In vivo rates of all-trans-retinal reduction and 11-cis-retinal formation during recovery from bleaching were similar in Rdh12-deficient and wild-type mice matched for an Rpe65 polymorphism that impacts visual cycle efficiency. However, retinal homogenates from Rdh12-deficient mice exhibited markedly decreased capacity to reduce exogenous retinaldehydes in vitro. Furthermore, in vivo levels of the bisretinoid compound diretinoid-pyridinium-ethanolamine (A2E) were increased in Rdh12-deficient mice of various genetic backgrounds. Conversely, in vivo levels of retinoic acid and total retinol were significantly decreased. Rdh12 transcript levels in wild-type mice homozygous for the Rpe65-Leu(450) polymorphism were greater than in Rpe65-Met(450) mice and increased during postnatal development in wild-type mice and Nrl-deficient mice having an all-cone retina. Rdh12-deficient mice did not exhibit increased retinal degeneration relative to wild-type mice at advanced ages, when bred on the light-sensitive BALB/c background, or when heterozygous for a allele of superoxide dismutase 2 (Sod2(+/-)). Our findings suggest that a critical function of RDH12 is the reduction of all-trans-retinal that exceeds the reductive capacity of the photoreceptor outer segments.
URI
http://www.jbc.org/content/early/2009/06/08/jbc.M109.020966.abstracthttp://repository.hanyang.ac.kr/handle/20.500.11754/76272
ISSN
0021-9258
DOI
10.1074/jbc.M109.020966
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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