Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium: implications for the process of drusen formation

Am J Ophthalmol. 2001 Jun;131(6):767-81. doi: 10.1016/s0002-9394(00)00961-2.


Purpose: The inheritance of specific apolipoprotein E allelles has been linked to atherosclerosis, Alzheimer disease, and, most recently, to the incidence of age-related macular degeneration. Apolipoprotein E is a common component of the extracellular plaques and deposits characteristic of these disorders, including drusen, which are a hallmark of age-related macular degeneration. Accordingly, we assessed the potential biosynthetic contribution of local ocular cell types to the apolipoprotein E found in drusen.

Methods: We measured apolipoprotein E mRNA levels in human donor tissues using a quantitative assay of apolipoprotein E transcription, and we localized apolipoprotein E protein to specific cell types and compartments in the neural retina, retinal pigmented epithelium, and choroid using laser scanning confocal immunofluorescence microscopy.

Results: Apolipoprotein E immunoreactivity is associated with photoreceptor outer segments, the retinal ganglion cell layer, the retinal pigmented epithelium basal cytoplasm and basal lamina, and with both collagenous layers of Bruch membrane. Apolipoprotein E appears to be a ubiquitous component of drusen, irrespective of clinical phenotype. It also accumulates in the cytoplasm of a subpopulation of retinal pigmented epithelial cells, many of which overlie or flank drusen. Mean levels of apolipoprotein E mRNA in the adult human retina are 45% and 150% of the levels measured in liver and adult brain, the two most abundant biosynthetic sources of apolipoprotein E. Apolipoprotein E mRNA levels are highest in the inner retina, and lowest in the outer retina where photoreceptors predominate. Significant levels of apolipoprotein E mRNA are also present in the retinal pigmented epithelium/choroid complex and in cultured human retinal pigmented epithelial cells.

Conclusions: Apolipoprotein E protein is strategically located at the same anatomic locus where drusen are situated, and the retinal pigmented epithelium is the most likely local biosynthetic source of apolipoprotein E at that location. Age-related alteration of lipoprotein biosynthesis and/or processing at the level of the retinal pigmented epithelium and/or Bruch membrane may be a significant contributing factor in drusen formation and age-related macular degeneration pathogenesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Aged
  • Apolipoproteins E / genetics
  • Apolipoproteins E / metabolism*
  • Bruch Membrane / metabolism
  • Cells, Cultured
  • Choroid / metabolism
  • Fluorescent Antibody Technique
  • Humans
  • Microscopy, Confocal
  • Middle Aged
  • Pigment Epithelium of Eye / cytology
  • Pigment Epithelium of Eye / metabolism*
  • RNA, Messenger / metabolism
  • Retina / cytology
  • Retina / metabolism*
  • Retinal Drusen / etiology
  • Retinal Drusen / metabolism
  • Rod Cell Outer Segment / metabolism
  • Tissue Distribution


  • Apolipoproteins E
  • RNA, Messenger