Aging, age-related macular degeneration, and the response-to-retention of apolipoprotein B-containing lipoproteins

Prog Retin Eye Res. 2009 Nov;28(6):393-422. doi: 10.1016/j.preteyeres.2009.08.001. Epub 2009 Aug 19.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Aging*
  • Animals
  • Apolipoproteins B / genetics
  • Apolipoproteins B / metabolism*
  • Bruch Membrane / metabolism
  • Bruch Membrane / pathology
  • Bruch Membrane / ultrastructure
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / metabolism
  • Cardiovascular Diseases / pathology
  • Cholesterol / metabolism
  • Disease Models, Animal
  • Humans
  • Lipoproteins / metabolism*
  • Lipoproteins / ultrastructure
  • Macular Degeneration* / epidemiology
  • Macular Degeneration* / etiology
  • Macular Degeneration* / genetics
  • Macular Degeneration* / pathology
  • Models, Biological
  • Pigment Epithelium of Eye / metabolism
  • Pigment Epithelium of Eye / pathology
  • Pigment Epithelium of Eye / ultrastructure
  • Retina / anatomy & histology
  • Retina / ultrastructure
  • Risk Factors


  • Apolipoproteins B
  • Lipoproteins
  • Cholesterol