Compelling evidence from epidemiological and laboratory studies suggests that light toxicity plays a role in the development of age-related pathology in the retina; however, an important unresolved issue concerns the dependence of retinal damage on exposure wavelength. The overall goal of the proposed research is to test the hypothesis that different spectral classes of light damage exist, and that they can be distinguished by separate effects and mechanisms. Using methodology by which albino and pigmented rats are exposed to light of precisely defined wavelength, photon dose, and field uniformity, and a multidisciplinary approach for assessing light-induced changes in their retinas, the specific objectives of this research are to identify spectral classes of light damage on the basis of 1) action spectra determination and morphologic observation; 2) alterations in rhodopsin levels and regeneration kinetics; 3) downregulation of opsin synthesis; 4) the role of apoptosis in photoreceptor and retinal pigment epithelial cell death; and 5) involvement of oxidative mechanisms and a protective role for beta- carotene. The proposed studies will provide important information regarding the effects and mechanisms of retinal phototoxicity which could help to clarify its role in retinal aging. Furthermore, this information should be useful for devising recommendations aimed at preventing light-induced retinal pathology by filtering out specific wavelengths of light, and by providing adequate protection against light-induced oxidation. These measures may he of paramount importance considering recent epidemiological evidence suggesting that cumulative sunlight exposure is associated with increased risk for acquiring age-related macular degeneration (AMD).
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