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H. Kochounian, E. Barron, H. K. W. Fong; Retinal Pigment Epithelium Contribution to the Protein Component of Drusen and Age-Related Extracellular Deposits. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1747.
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Human retinal pigment epithelial (RPE) cells, the sub-RPE space, Bruch's membrane and choriocapillaris undergo prominent aging changes not seen in most other mammals. In elderly eyes, age-related deposits may accumulate on both sides of the RPE basement membrane. The origin of the age-related material in Bruch's membrane is thought to include the RPE. Human RPE cells synthesize an extraneous splice isoform of the retinal G protein-coupled receptor (RGR), and an epitope of this exon-skipping protein variant (RGR-d) is released from the RPE into Bruch's membrane in young and old persons. The purpose of this work is to investigate the presence of extracellular RGR-d in drusen and age-related deposits in Bruch's membrane. We investigated the different types of drusen in which the RGR-d epitope is present and analyzed what types of organelle or structure, if any, are associated with RGR-d at the ultrastructural level.
RGR-d was analyzed in human donor eyes by immunohistochemical localization at the light and electron microscopic levels. Pre-embed immunohistochemical localization at the electron microscopic level was performed by peroxidase-based detection of electron dense diaminobenzidine reaction product.
We have shown that extracellular RGR-d is present in most types of drusen, including hard, soft, large confluent and early-stage drusen. We have demonstrated the presence of the RGR-d epitope in vesicular deposits (diameter ~100 nm) and membranous debris in the inner collagenous zone and intercapillary regions at the electron microscopic level.
These results confirm that particular extracellular deposits in Bruch's membrane indeed originate from the RPE. RGR-d, an RPE-specific marker, is a constituent not only of various types of drusen, but of basal linear deposits consisting of a diffuse layer of vesicular and planar material external to the RPE basement membrane.
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