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V. Luibl, M. Isas, C. Glabe, R. Kayed, J. Chen, R. Langen; Similarities between AMD and amyloid diseases suggested by the presence of toxic, amyloidogenic oligomers in drusen . Invest. Ophthalmol. Vis. Sci. 2004;45(13):1789.
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Purpose: To test for similarities between age–related macular degeneration (AMD) and amyloid diseases, such as Alzheimer’s and Parkinson’s diseases. Our intent was to determine whether toxic oligomers, which are characteristic of amyloid diseases, are also present in drusen. Methods: Frozen tissue sections from human donor eyes were incubated with the conformationally specific anti–oligomer antibody, which recognizes toxic oligomers derived from a variety of amyloid proteins (Kayed et al.; Science, 2003 April 18). Subsequently, the tissue sections were incubated with a fluorescent–labeled secondary antibody and visualized with a confocal microscope (Zeiss LSM 510). In addition, ELISA assays were performed on extracts derived from neural retina, as well as on extracts derived from RPE/Bruch’s membrane that contained drusen. Results: All human eyes with drusen were labeled with the anti–oligomer antibody. Labeling was observed within the core of some, but not all, drusen. The labeled cores were located in juxtaposition to Bruch’s membrane, and were not larger than 15 µm in size. No labeling was detected in control age–matched eyes without drusen. Labeling was specific because it was blocked when the anti–oligomer antibody was pre–incubated with prepared oligomeric species of the aß peptide. ELISA assays further confirmed the presence of oligomeric species in extracts derived from RPE/Bruch’s membrane containing drusen, but not in extracts derived from neural retina obtained from the same eye. Conclusions: Our results have revealed the presence of toxic oligomeric species in drusen, indicating that protein misfolding is likely to be involved in the biogenesis of drusen. It is quite possible that said species has a toxic effect on RPE cells, and thus represents a primary pathogenic stimulus.
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