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KA Howes, B Schmidt, J Church-Kopish, S Pulukuri, JM Frederick, A Sitaramayya, A Marks, W Baehr; AMD-Like Retinal Degeneration in S100B Transgenic Mice . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2812.
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Purpose:S100B, previously identified as CD-GCAP (calcium-dependent guanylate cyclase activating protein), is thought to regulate the activity of a membrane-bound guanylate cyclase in photoreceptor cells at high [Ca2+]. It is highly probable, however, that S100B serves additional functions in retina consistent with its selective expression in this tissue. S100B transgenic mice were generated originally to study effects of S100B overexpression on CNS development and function. In this respect, it is interesting that elevated levels of S100B may contribute to neuronal degeneration in the age-related Alzheimer's disease. Our study examines the effect of S100B overexpression on retinal tissue with the aim of identifying additional S100B targets. Methods:RPE/retinas from S100B transgenic and age-matched control mice were compared by histology, confocal microscope immunocytochemistry, and immunoblot analyses. Results:S100B transgenic mice (from 2 to 6 months) show intense immunolocalization of S100B in RPE unlike wild-type mice. Peripheral RPE regions appear healthy, suggesting that S100B accumulation in itself does not affect cell viability. Unlike age-matched controls, autofluorescent granules accumulate in 2-month old transgenic RPE cells and by 6 months, RPE cells are packed with granules. Correspondingly, 2-month old transgenic mice show no overt photoreceptor cell pathology, but 6-month old S100B transgenic mice show loss of photoreceptors, loss of RPE cells, disorganization of outer segments, and subretinal tears. Conclusion:S100B transgenic mice reveal a retinal degeneration arising from perturbation of the RPE/choroid and loss of photoreceptors from the retina in a central-to-peripheral gradient. Additionally, autofluorescent granule accumulation in RPE cells, outer segment disorganization and subretinal tears are observed. The S100B transgenic mice are the first promising animal model for human AMD (age-related macular degeneration). Further studies in these mice will determine their usefulness in understanding the pathogenesis of AMD and designing therapeutic approaches to prevention and treatment of this disease.
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