Rdh12 Activity and Effects on Retinoid Processing in the Murine Retinaopen access
- Authors
- Chrispell, Jared D.; Feathers, Kecia L.; Kane, Maureen A.; Kim, Chul Y.; Brooks, Matthew; Khanna, Ritu; Kurth, Ingo; Huebner, Christian A.; Gal, Andreas; Mears, Alan J.; Swaroop, Anand; Napoli, Joseph L.; Sparrow, Janet R.; Thompson, Debra A.
- Issue Date
- Aug-2009
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- All-trans retinol; Congenital Amaurosis; Lipofuscin; Nrl; RDH12; RPE65; Retinoic Acid; Short Chain Dehydrogenase/Reductase
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.284, no.32, pp.21468 - 21477
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Volume
- 284
- Number
- 32
- Start Page
- 21468
- End Page
- 21477
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/40968
- DOI
- 10.1074/jbc.M109.020966
- ISSN
- 0021-9258
- 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 null 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.
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