Suppression of constant-light-induced blindness but not retinal degeneration by inhibition of the rhodopsin degradation pathway

Curr Biol. 2004 Dec 14;14(23):2076-85. doi: 10.1016/j.cub.2004.11.054.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arrestin / genetics
  • Blindness / genetics*
  • Blindness / physiopathology
  • Calcium-Binding Proteins / genetics
  • Drosophila Proteins / genetics
  • Drosophila melanogaster
  • Electroretinography
  • Light / adverse effects*
  • Microscopy, Electron, Transmission
  • Models, Biological
  • Mutation / genetics*
  • Phosphoprotein Phosphatases / genetics
  • Photoperiod
  • Photoreceptor Cells, Invertebrate / ultrastructure
  • Proteins / metabolism
  • Retinal Degeneration / etiology*
  • Retinal Degeneration / physiopathology
  • Rhodopsin / genetics
  • Rhodopsin / metabolism*


  • Arrestin
  • Calcium-Binding Proteins
  • Drosophila Proteins
  • Proteins
  • lysosomal proteins
  • Rhodopsin
  • Phosphoprotein Phosphatases
  • rdgC protein, Drosophila