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PL Eversole-Cire, W Hao, C-K Chen, NV Kransnoperova, MI Simon, J Lem; Evidence for Two Pathways Leading to Light-Induced Retinal Degeneration . Invest. Ophthalmol. Vis. Sci. 2002;43(13):3719.
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Purpose: Emerging evidence suggests that activated rhodopsin mediates the damaging effects of light leading to retinal degeneration. For example, mice with defects in rhodopsin inactivation [rhodopsin kinase deficient (Rhok-/-) and arrestin deficient (Arr-/-) mice] demonstrate an increased sensitivity to light-induced retinal damage. To determine if prolonged signaling of the phototransduction cascade in these mutant mice is responsible for the increase in light sensitivity, Rhok-/- and Arr-/- mice were crossed to mice in which signaling through the phototransduction cascade was blocked [G-protein transducin deficient (Gnat1-/-) mice] and the susceptibility to light damage compared. Methods: Dark-reared mice were exposed to 2000 lux of white fluorescent light for various periods of time to assess effects of moderate light exposure. Mice were also exposed to 6000 lux for 1 hour after pupil dilation followed by 24-hour dark-adaptation to determine the effects of acute high light exposure on the retina. Light-induced apoptosis was assessed by retinal morphology and quantified using an oligonucleosome release ELISA. Results: Rhok-/- and Arr-/- mice were highly sensitive to light and irridiation results in extended activation of rhodopsin even at low light dosages. Rhok-/-/Gnat1-/- and Arr-/-/Gnat1-/- were rescued from the damaging effects of moderate light exposure. However, in mice exposed to high light levels retinal damage was not prevented in the Gnat1-/- background but was prevented in the c-fos-/- background as shown by Hafezi et al. Conclusion: These results indicate that light induced retinal damage can proceed through at least two different pathways; one pathway that is dependent on c-fos and a second pathway that is dependent on a signaling event downstream of transducin in the phototransduction cascade.
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