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

Seung Jae Lee, Craig Montell

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)2076-2085
Number of pages10
JournalCurrent Biology
Volume14
Issue number23
DOIs
StatePublished - Dec 14 2004

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Retinal Degeneration
rhodopsin
Rhodopsin
blindness
Blindness
Light
Degradation
degradation
Vision Disorders
arrestins
Arrestin
mutation
Mutation
Wild Animals
fruit flies
Fruits
Drosophila melanogaster
Lighting
Phosphoric Monoester Hydrolases
Diptera

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)

Cite this

Suppression of constant-light-induced blindness but not retinal degeneration by inhibition of the rhodopsin degradation pathway. / Lee, Seung Jae; Montell, Craig.

In: Current Biology, Vol. 14, No. 23, 14.12.2004, p. 2076-2085.

Research output: Contribution to journalArticle

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