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. 2022 Jan 28;38(1):3–32. doi: 10.1089/jop.2021.0067

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© Michael Landowski and Catherine Bowes Rickman 2022; Published by Mary Ann Liebert, Inc.

This Open Access article is distributed under the terms of the Creative Commons License [CC-BY] (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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FIG. 1. — Association of dysregulated lipid metabolism with AMD development and progression. Left: Normal, healthy retina. Middle: Retina with signs of benign aging such as loss of mitochondria, RPE pigmentary changes, and BLamD formation between the RPE and BrM. Right: Through a complex interplay between genetic variants and environmental factors, AMD can develop and progress in the aging retina. Classic pathological hallmarks of AMD include recruitment of subretinal immune cells, photoreceptor degeneration, RPE atrophy and loss, drusen (which start out as basal linear deposits), and form within the ICL of BrM, choroidal atrophy, and CNV. Genetic and epidemiological studies of AMD patients revealed dysregulated lipid transport and metabolism as a key pathobiological mechanism behind AMD. Coding variants in APOE, LIPC, CETP, LPL, and ABCA1 are associated with AMD risk, but it is still unknown why particular variants are linked with disease risk. In addition, diets enriched in omega-6 fatty acids while those deficient in omega-3 fatty acids also increase an individual's risk for AMD. It is widely accepted that omega-6 fatty acids promote, and omega-3 fatty acids dampen retinal inflammation. ABCA1, ATP-binding cassette subfamily A member 1; AMD, age-related macular degeneration; APOE, Apolipoprotein E; BI, basal infoldings; BLamD, basal laminar deposit; BrM, Bruch's membrane; CETP, cholesteryl ester transfer protein; Choroid BM, choroid basement membrane; CNV, choroidal neovascularization; EL, elastic layer; ICL, inner collagenous layer; LD, lipid droplet; LIPC, hepatic lipase; LPL, lipoprotein lipase; M, mitochondria; N, nucleus; OCL, outer collagenous layer; PG, pigment granule; Ph, phagosome; RPE BM, RPE basement membrane; RPE, retinal pigmented epithelium.