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H.S. Ying, R.R. Grebe, M. Mahmoud, S.Y. Kim, J.T. Handa, E. de Juan; Genistein reduces retinal pigment epithelial and Bruch’s membrane degeneration induced by prolonged blue light exposure in senescence–accelerated mice. . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1809.
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Purpose: To determine whether genistein can ameliorate the effect of blue (410nm) light exposure for 52 weeks in a murine model of accelerated aging. Methods: 190 senescence–accelerated mice (SAM) strain P8 (prone) or R1(resistant) were housed in a pathogen–free microisolation facility until 0 to 4 weeks of age and then continuously exposed to either blue light or white light for 52 weeks. The mice were fed ad libitum with Clinton/Cybulski chow with or without added genistein (300mg/4057 kcal food) and with or without added fat (40kcal%). The mice were sacrificed at the end of the exposure period and arbitrarily selected eyes were examined by transmission electron microscopy. A semi–quantitative grading system was used to evaluate the characteristics, severity, and frequency of basal laminar deposit (BLD) formation (Cousins, et al. Exp. Eye Res. 2002; 75:543–553). Results: Electron microscopy revealed rare BLD in the SAM R1 strain with mild to moderate Bruch’s membrane (BrM) thickening even after blue light exposure. Aged SAM P8 strain developed only mild to moderate BLD when exposed to white light but developed moderate to severe BLD when exposed to blue light. Blue light exposure was also associated with broadening and reduction of the basal infoldings and cytoplasmic vacuolization in the retinal pigment epithelial (RPE) cells, thickening of BrM, especially the inner collagenous layer, and widening of the intercapillary septa. Co–administration of genistein reduced the frequency and severity of the degenerative RPE and BrM changes induced by blue light exposure but appeared to have less effect on BLD formation. Conclusions: We previously reported that the SAM P8 strain exhibits abnormal RPE and BrM changes at 52 weeks of age. Here, we found that these changes were exacerbated by continuous blue light administration for 52 weeks duration and that this exacerbation could be ameliorated by orally administered genistein. This refinement of an animal model of accelerated aging may provide a useful basis for future studies of human diseases such as age–related macular degeneration.
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