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S. Umeda, M.T. Suzuki, H. Okamoto, F. Ono, K. Terao, A. Mizota, Y. Yoshikawa, Y. Tanaka, T. Iwata; Molecular Composition of Drusen Observed in Hereditary Macular Degeneration in Cynomolgus Monkey (Macaca Fascicularis): Similarities to Age–Related Macular Degeneration in Human . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3011.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To characterize molecular composition of drusen observed in a heredidary macular degeneration in a monkey pedigree, in comparison with that observed in elder monkeys and in human AMD. Methods: Funduscopic and histologic examinations were performed on family members in the pedigree for inherited form macular degeneration, and on 278 aged monkeys (mean age = 16.94 y) for age–related form of the disease. The molecular composition of drusen was analyzed by immunohistochemical method and/or direct proteomic approach using liquid chromatography tandem MS (LC–MS/MS). Results: Drusen in both inherited and age–related forms of macular degeneration showed immunoreactivities for apolipoprotein E, amyloid P component, complement component C5, the terminal C5b–9 complement complex, vitronectin, and membrane cofactor protein. LC–MS/MS analyses identified 60 proteins as constituents of drusen, including a number of common components with drusen in AMD, such as annexins, crystallins, immunoglobulins, and complement components. Conclusions: Monkey drusen both in age–related and inherited forms of macular degeneration had common components with AMD drusen, indicating that chronic inflammation mediated by complement activation might be also involved in the formation of drusen in these diseases. The results suggest that isolation of the disease–causing gene for inherited form could offer important clues to reveal the causal event that triggers drusen formation, and might provide new candidate locus for AMD.
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