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Illuminating an Arrestin Pathway to Blindness

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Science's STKE  21 Dec 2004:
Vol. 2004, Issue 264, pp. tw456
DOI: 10.1126/stke.2642004tw456

Using Drosophila as a model system, Lee and Montell uncovered a surprising divergence between the pathway leading to light-induced blindness and that underlying retinal degeneration. In many vertebrates, sustained exposure to even low-intensity light leads to blindness, which has long been attributed to the retinal degeneration that takes place under these conditions. Lee and Montell showed that Drosophila exposed to continuous light also displayed a progressive reduction in the visual response (measured with an electroretinogram), as well as retinal degeneration. The photoresponse was substantially reduced after 9 days of exposure to continuous light and drastically reduced--or abolished--after 17 days of exposure. Western analysis of head extracts indicated that the concentration of Rh1, the major rhodopsin, declined in parallel with attenuation of the photoresponse, whereas that of various other signaling proteins did not. Genetic analysis revealed that mutations in arrestin (which encodes a protein implicated in rhodopsin inactivation) and sunglasses (which encodes a lysosomal protein enriched in photoreceptors) suppressed both light-induced blindness and the decrease in Rh1 concentration, whereas a mutation in rhodopsin phosphatase enhanced both of these effects. However, mutations in arrestin, sunglasses, or rh1 (which also suppressed light-induced blindness) failed to suppress retinal degeneration, whereas genetic manipulations that suppress retinal degeneration failed to mitigate light-induced blindness. Continuous light increased the concentration of rhodopsin-arrestin complexes, whereas mutations that suppressed light-induced blindness decreased their concentration. Thus, the authors conclude that light-induced blindness and light-induced retinal degeneration occur through distinct molecular mechanisms and that the former involves rhodopsin degradation through an arrestin-dependent pathway.

S.-J. Lee, C. Montell, Suppression of constant-light-induced blindness but not retinal degeneration by inhibition of the rhodopsin degradation pathway. Current Biol. 14, 2076-2085 (2004). [Online Journal]

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