Suppression of constant-light-induced blindness but not retinal degeneration by inhibition of the rhodopsin degradation pathway
Suppression of constant-light-induced blindness but not retinal degeneration by inhibition of the rhodopsin degradation pathway
复制标题
DOI：
10.1016/j.cub.2004.11.054
复制
发表时间：
2004-12-14
期刊：
影响因子：
9.2
通讯作者：
Montell, C
中科院分区：
文献类型：
--
作者：
Lee, SJ;Montell, C
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.
