Retinol dehydrogenase (RDH12) protects photoreceptors from light-induced degeneration in mice.
RDH12 has been suggested to be one of the retinol dehydrogenases (RDH) involved in the vitamin A recycling system (visual cycle) in the eye. Loss of function mutations in the RDH12 gene were recently reported to be associated with autosomal recessive childhood-onset severe retinal dystrophy. Here we show that RDH12 localizes to the photoreceptor inner segments and that deletion of this gene in mice slows the kinetics of all-trans-retinal reduction, delaying dark adaptation. However, accelerated 11-cis-retinal production and increased susceptibility to light-induced photoreceptor apoptosis were also observed in Rdh12(-/-) mice, suggesting that RDH12 plays a unique, nonredundant role in the photoreceptor inner segments to regulate the flow of retinoids in the eye. Thus, severe visual impairments of individuals with null mutations in RDH12 may likely be caused by light damage(1).
Maeda
Akiko
A
Department of Pharmacology and Ophthalmology, Case Western Reserve University, Cleveland, Ohio 44106, USA.
Maeda
Tadao
T
Imanishi
Yoshikazu
Y
Sun
Wenyu
W
Jastrzebska
Beata
B
Hatala
Denise A
DA
Winkens
Huub J
HJ
Hofmann
Klaus Peter
KP
Janssen
Jacques J
JJ
Baehr
Wolfgang
W
Driessen
Carola A
CA
Palczewski
Krzysztof
K
D000429:Alcohol Oxidoreductases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers / Q000235:genetics; D004596:Electroretinography; D005260:Female; D006801:Humans; D008027:Light / Q000009:adverse effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D020419:Photoreceptor Cells, Vertebrate / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects; D012162:Retinal Degeneration / Q000201:enzymology* / Q000235:genetics / Q000473:pathology / Q000517:prevention & control; D012176:Retinoids / Q000378:metabolism
D017931:DNA Primers; D012176:Retinoids; D000429:Alcohol Oxidoreductases; C489649:RDH12 protein, human; C022520:retinol dehydrogenase