title: Suppression of constant-light-induced blindness but not retinal degeneration by inhibition of the rhodopsin degradation pathway.
abstract: BACKGROUND
  Continuous exposure to light, even at relatively low intensities, leads to retinal damage and blindness in wild-type animals. However, the molecular mechanisms underlying constant-light-induced blindness are poorly understood. It has been presumed that the visual impairment resulting from long-term, continuous exposure to ambient light is a secondary consequence of the effects of light on retinal morphology, but this has not been addressed.
  
  
  RESULTS
  To characterize the mechanism underlying light-induced blindness, we applied a molecular genetic approach using the fruit fly, Drosophila melanogaster. We found that the temporal loss of the photoresponse was paralleled by a gradual decline in the concentration of rhodopsin. The decline in rhodopsin and the visual response were suppressed by a C-terminal truncation of rhodopsin, by mutations in arrestin, and by elimination of a lysosomal protein, Sunglasses. Conversely, the visual impairment was greatly enhanced by mutation of the rhodopsin phosphatase, rdgC. Surprisingly, the mutations that suppressed light-induced blindness did not reduce the severity of the retinal degeneration resulting from constant light. Moreover, mutations known to suppress retinal degeneration did not ameliorate the light-induced blindness.
  
  
  CONCLUSIONS
  These data demonstrate that the constant light-induced blindness and retinal degeneration result from defects in distinct molecular pathways. Our results support a model in which visual impairment caused by continuous illumination occurs through an arrestin-dependent pathway that promotes degradation of rhodopsin.
authors.affiliation: Department of Biological Chemistry, The Johns Hopkins University School of Medicine, Baltimore, MD 21205 USA.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Lee
authors.forename: Craig
authors.initials: C
authors.lastname: Montell
mesh_terms: D000818:Animals; D019393:Arrestin / Q000235:genetics; D001766:Blindness / Q000235:genetics* / Q000503:physiopathology; D002135:Calcium-Binding Proteins / Q000235:genetics; D029721:Drosophila Proteins / Q000235:genetics; D004331:Drosophila melanogaster; D004596:Electroretinography; D008027:Light / Q000009:adverse effects*; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D009154:Mutation / Q000235:genetics*; D010749:Phosphoprotein Phosphatases / Q000235:genetics; D017440:Photoperiod; D017956:Photoreceptor Cells, Invertebrate / Q000648:ultrastructure; D011506:Proteins / Q000378:metabolism; D012162:Retinal Degeneration / Q000209:etiology* / Q000503:physiopathology; D012243:Rhodopsin / Q000235:genetics / Q000378:metabolism*
chemical_list: D019393:Arrestin; D002135:Calcium-Binding Proteins; D029721:Drosophila Proteins; D011506:Proteins; C018589:lysosomal proteins; D012243:Rhodopsin; D010749:Phosphoprotein Phosphatases; C074643:rdgC protein, Drosophila