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JW Ruberti, CA Curcio, L Millican, BP M Menco, J-D Huang, M Johnson; An Age Related 'Lipid Wall' in Human Bruch's Membrane . Invest. Ophthalmol. Vis. Sci. 2002;43(13):2785.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: 1) To examine the detailed ultrastructure of Bruch's membrane in young and old human eyes using Quick Freeze Deep Etch (QFDE) electron microscopy. 2) To characterize the accumulated lipids in Bruch's membrane and the extracellular matrix (ECM) that surrounds them. Methods: The ultrastructure of the ECM of grossly normal macular Bruch's membrane of young (27 and 41 yo) and old (76 and 78 yo) human eyes was examined. The eyes were fixed within 4 hours of death and processed for either QFDE or standard transmission electron microscopy. Results: In older eyes, lipid rich particles (LRPs) from 30 to 170 nm in diameter (mean 70-80 nm) appear to accumulate extensively and associate with the ECM of the region subjacent to the basal lamina (BL) of the retinal pigment epithelium (RPE). Such particles have been identified previously as esterified-cholesterol-rich by Curcio et al., (IOVS 42:265, 2001). The material between the LRPs is electron-dense and apparently fibrillar. There was little intrusion of the LRPs into the BL itself. In one of the two older eyes, the layer of LRP's below the RPE BL formed a nearly confluent 'wall'. Conclusion: Bruch's membrane sits between the outer retina and its primary metabolic source and sink. Empirically measured hydraulic conductivity decreases substantially with age. The link between permeability decrease and lipid accumulation has not yet been proven, however, our investigations demonstrate that LRPs preferentially accumulate in the thin region external to the RPE BL forming a 'Lipid Wall'. Such a wall may prevent transport of hydrophilic materials through Bruch's. Understanding the physicochemical phenomena that drive the nucleation and accumulation of these LRPs may shed some light on how age- and disease-related change in Bruch's membrane can impact retinal function.
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