期刊
PROGRESS IN RETINAL AND EYE RESEARCH
卷 28, 期 6, 页码 393-422出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.preteyeres.2009.08.001
关键词
Age-related macular degeneration; Retinal pigment epithelium; Bruch's membrane; Drusen; Basal deposits; Lipoproteins; Cholesterol; Retinyl ester; Apolipoprotein B
资金
- NIH [EY06109, EY014662]
- International Retinal Research Foundation
- American Health Assistance Foundation
- EyeSight Foundation of Alabama
- Research to Prevent Blindness, Inc.
- Macula Vision Research Foundation
- Roger Johnson Prize in Macular Degeneration Research
- Deutsche Forschungsgemeinschaft
The largest risk factor for age-related macular degeneration (ARMD) is advanced age. A prominent age-related change in the human retina is the accumulation of histochemically detectable neutral lipid in normal Bruch's membrane (BrM) throughout adulthood. This change has the potential to have a major impact on physiology of the retinal pigment epithelium (RPE). It occurs in the same compartment as drusen and basal linear deposit, the pathognomonic extracellular, lipid-containing lesions of ARMD. Here we present evidence from light microscopic histochemistry, ultrastructure, lipid profiling of tissues and isolated lipoproteins, and gene expression analysis that this deposition can be accounted for by esterified cholesterol-rich, apolipoprotein B-containing lipoprotein particles constitutively produced by the RPE. This work collectively allows ARMD lesion formation and its aftermath to be conceptualized as a response to the retention of a sub-endothelial apolipoprotein B lipoprotein, similar to a widely-accepted model of atherosclerotic coronary artery disease (CAD) (Tabas et al., 2007). This approach provides a wide knowledge base and sophisticated clinical armamentarium that can be readily exploited for the development of new model systems and the future benefit of ARMD patients. (C) 2009 Published by Elsevier Ltd.
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