Thematic Review
Apolipoprotein B-containing lipoproteins in retinal aging and age-related macular degeneration

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The largest risk factor for age-related macular degeneration (ARMD) is advanced age. With aging, there is a striking accumulation of neutral lipids in Bruch's membrane (BrM) of normal eye that continues through adulthood. This accumulation has the potential to significantly impact the physiology of the retinal pigment epithelium (RPE). It also ultimately leads to the creation of a lipid wall at the same locations where drusen and basal linear deposit, the pathognomonic extracellular, lipid-containing lesions of ARMD, subsequently form. Here, we summarize evidence obtained from light microscopy, ultrastructural studies, lipid histochemistry, assay of isolated lipoproteins, and gene expression analysis. These studies suggest that lipid deposition in BrM is at least partially due to accumulation of esterified cholesterol-rich, apolipoprotein B-containing lipoprotein particles produced by the RPE. Furthermore, we suggest that the formation of ARMD lesions and their aftermath may be a pathological response to the retention of a sub-endothelial apolipoprotein B lipoprotein, similar to a widely accepted model of atherosclerotic coronary artery disease (Tabas, I., K. J. Williams, and J. Borén. 2007. Subendothelial lipoprotein retention as the initiating process in atherosclerosis: update and therapeutic implications. Circulation. 116:1832–1844). This view provides a conceptual basis for the development of novel treatments that may benefit ARMD patients in the future.

retinal pigment epithelium
Bruch's membrane
drusen
basal deposits
cholesterol
retinyl ester

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This work was supported by the National Institutes of Health grants EY06109 and EY014662, the International Retinal Research Foundation, the American Health Assistance Foundation, the EyeSight Foundation of Alabama, Research to Prevent Blindness, Inc., the Macula Vision Research Foundation, the Roger Johnson Prize in Macular Degeneration Research, and Deutsche Forschungsgemeinschaft. Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the National Institutes of Health.

    Abbreviations:

    apo

    apolipoprotein

    ARMD

    age-related macular degeneration

    BlamD

    basal laminar deposit

    BlinD

    basal linear deposit

    BrM

    Bruch's membrane

    CAD

    coronary artery disease

    CM

    chylomicron

    EC

    esterified cholesterol

    HBL

    hypobetalipoproteinemia

    MTP

    microsomal triglyceride transfer protein

    OTAP

    osmium-tannic acid-paraphenylenediamine

    QFDE

    quick-freeze/deep-etch

    RPE

    retinal pigment epithelium

    TG

    triglyceride

    UC

    unesterified cholesterol

2

A retinal degeneration with thick basal deposits in an HBL patient is now considered late onset retinal degeneration, which segregated separately from HBL (119, 121, 122).