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P.T. Johnson, G.P. Lewis, K.C. Talaga, M. Brown, P.J. Kappel, D.H. Anderson, S.K. Fisher, L.V. Johnson; Drusen Exert Degenerative Effects on Adjacent Retinal Cells . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1723.
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Purpose: Drusen are variably sized extracellular deposits that form between the retinal pigmented epithelium (RPE) and Bruch's membrane. Numerous and/or confluent drusen are a significant risk factor for age-related macular degeneration. The purpose of this study is to investigate the impact of drusen on overlying cells of the retina. Methods: Tissue containing retina and RPE/choroid was dissected from human donor eyes, embedded in agarose and sectioned at 100 microns using a vibratome. The sections were immunostained with antibodies against rod and cone opsins, second and third order neurons, and glial markers, then processed for confocal microscopy. Drusen were identified by immunostaining with antibodies against apolipoprotein E. Results: Retinal cells that overlie both soft and hard drusen exhibit numerous structural and molecular abnormalities. Normally detectable only in the outer segments of rod photoreceptors, rod opsin immunolabeling is also observed in the inner segment, cell body, axon and axon terminal of photoreceptors that overlie drusen. Labeling with this antibody also reveals the deflection and shortening of rod outer segments. Cone photoreceptors, immunostained with SWS- and MWS-cone opsin antibodies, display similar structural abnormalities as well as the decreased expression of cone opsin proteins. Hypertrophy of Müller glia is also associated with drusen. These cells upregulate the expression of intermediate filament proteins (vimentin and GFAP) in areas of retina overlying drusen. In contrast, bipolar, horizontal, amacrine, and ganglion cells all appear unaffected. These molecular and cellular abnormalities are confined to retinal regions directly overlying and immediately adjacent to drusen; whereas more distant retinal regions appear unperturbed. Remarkably, significant abnormalities are also observed over very small (<60 micron diameter), subclinical drusen. Conclusions: These data show that both soft and hard drusen induce cellular and molecular abnormalities in the overlying retina that resemble degenerative changes observed in experimental retinal detachments. The observations suggest that considerable localized damage to retinal photoreceptors, as well as the activation of Müller glial cells, occurs as a consequence of drusen formation.
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