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R.F. Mullins, M.H. Kuehn, N. Aptsiauri, G.S. Hageman; Distribution of Terminal Complement Complexes at the RPE-Choriocapillaris Interface in Age-Related Macular Degeneration . Invest. Ophthalmol. Vis. Sci. 2003;44(13):4226.
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Purpose: To investigate the distribution of the terminal complement complex (C5b-9) at the RPE-choroid interface in age-related macular degeneration (AMD) and in normal aging. Methods: Eyes from 61 human donors were classified--based on age, clinical records, and gross and fundus photographs--into the following categories: young control (under 55 years of age, no maculopathy; n=13); age-matched control (>55 years of age, no maculopathy, n=18); age-related maculopathy (ARM; >55 years of age with macular drusen and/or pigmentary changes; n=10); and AMD (>55 years of age with advanced disease; n=20). Immunohistochemical labeling for the C5b-9 complement complex was performed using a monoclonal antibody and the degree of reactivity was evaluated from juxtamacular and equatorial photographs using a semiquantitative scale from 0 to 2. The following regions were scored: choriocapillaris; choriocapillary pillars; outer collagenous layer of Bruch’s membrane; and inner collagenous layer of Bruch’s membrane. In some cases, dual labeling confocal microscopy was performed to determine the extent of colocalization of complement complexes with extracellular matrix and/or cellular antigens. Soluble and membrane-associated levels of C5b-9 complexes were assayed in the RPE and choroid from 5 donors using ELISA. Results: A significant increase in C5b-9 immunoreactivity was observed in the space surrounding the macular choriocapillaris in donors with ARM and AMD, as compared to age-matched control donors. The majority of this labeling appears to be associated with the extracellular matrix, although some may be associated with the fenestrated surface of capillary endothelial cells. ELISA measurements show detectable levels of C5b-9 in the membrane fraction of cells from the choroid and the RPE. Conclusions: The macular choriocapillaris may initiate, or be a target for, complement attack in AMD.
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