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      Antecedents of Soft Drusen, the Specific Deposits of Age-Related Macular Degeneration, in the Biology of Human Macula


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          AMD pathobiology was irreversibly changed by the recent discovery of extracellular cholesterol-containing deposits in the subretinal space, between the photoreceptors and retinal pigment epithelium (RPE), called subretinal drusenoid deposits (SDDs). SDDs strikingly mirror the topography of rod photoreceptors in human macula, raising the question of whether an equivalent process results in a deposition related to foveal cones. Herein we propose that AMD's pathognomonic lesion—soft drusen and basal linear deposit (BLinD, same material, diffusely distributed)—is the leading candidate. Epidemiologic, clinical, and histologic data suggest that these deposits are most abundant in the central macula, under the fovea. Strong evidence presented in a companion article supports the idea that the dominant ultrastructural component is large apolipoprotein B,E–containing lipoproteins, constitutively secreted by RPE. Lipoprotein fatty acids are dominated by linoleate (implicating diet) rather than docosahexaenoate (implicating photoreceptors); we seek within the retina cellular relationships and dietary drivers to explain soft druse topography. The delivery of xanthophyll pigments to highly evolved and numerous Müller cells in the human fovea, through RPE, is one strong candidate, because Müller cells are the main reservoir of these pigments, which replenish from diet. We propose that the evolution of neuroglial relations and xanthophyll delivery that underlie exquisite human foveal vision came with a price, that is, soft drusen and sequela, long after our reproductive years.

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          Most cited references 193

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                Author and article information

                Invest Ophthalmol Vis Sci
                Invest. Ophthalmol. Vis. Sci
                Invest Ophthalmol Vis Sci
                Investigative Ophthalmology & Visual Science
                The Association for Research in Vision and Ophthalmology
                March 2018
                : 59
                : 4
                : AMD182-AMD194
                [1]Department of Ophthalmology and Visual Sciences, School of Medicine, University of Alabama at Birmingham, Birmingham, Alabama, United States
                Author notes
                Correspondence: Christine A. Curcio, Department of Ophthalmology and Visual Sciences, EyeSight Foundation of Alabama Vision Research Laboratories, 1670 University Boulevard Room 360, University of Alabama School of Medicine, Birmingham, AL 35294-0019, USA; christinecurcio@ 123456uabmc.edu .
                iovs-59-04-18 IOVS-18-24883
                Copyright 2018 The Authors

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.

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