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David P. Bingaman, Jasmine Hernandez, Carmelo Romano, Robert F. Mullins; Molecular Characterization of Subretinal Fibrosis in Human Eyes with AMD. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1762.
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Subretinal fibrosis (SRF) secondary to choroidal neovascularization (CNV) is associated with vision loss and possibly non-responsiveness to anti-VEGF therapies in age-related macular degeneration (AMD). Therefore, the molecular constituents of AMD-related SRF were investigated.
Human donor eyes (n=4) with SRF secondary to neovascular AMD were evaluated by lectin and immunohistochemistry, energy-dispersive X-ray spectroscopy (n=2), and pathology stains for a battery of markers directed against cellular and extracellular antigens.
Collagen I and IV showed robust labeling in SRF material, as did serum amyloid P component. In contrast to collagen IV, other basal lamina proteins (laminin and entactin) were restricted to blood vessel walls. Neither elastin nor complement complexes were detected. SRF lesions were PAS positive and Alcian blue reactive, consistent with the presence of mucopolysaccharides. The sialic acid-binding lectin, wheat germ agglutinin, also reacted strongly. Significant lipid staining with Sudan black B was not observed. No distinct signature was observed by X-ray analysis, although the elemental composition was distinct overall from aging Bruch’s membrane (such as a lower sulfur content). Labeling with antibodies directed against cellular markers excluded glial cells as major constituents, but IBA+ macrophages/microglia were routinely observed.
Subretinal fibrosis secondary to neovascular AMD has a distinct composition in human eyes that includes a restricted subset of basal lamina components, carbohydrate epitopes, and cell populations. Whether the extracellular material is derived from activated RPE, endothelial, connective tissue or immune cells remains to be determined. The types of collagen (I and IV) identified in the human samples were notably similar to those found in subretinal fibrotic membranes isolated from the mouse model of laser-induced CNV (data not shown).
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