Journal article
Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium: implications for the process of drusen formation
American journal of ophthalmology, Vol.131(6), pp.767-781
06/2001
DOI: 10.1016/S0002-9394(00)00961-2
PMID: 11384575
Abstract
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. 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. 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. 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.
Details
- Title: Subtitle
- Local cellular sources of apolipoprotein E in the human retina and retinal pigmented epithelium: implications for the process of drusen formation
- Creators
- Don H Anderson - Center for the Study of Macular Degeneration, Neuroscience Research Institute, University of California, Santa Barbara, California 93106, USA. d_anders@lifesci.ucsb.eduShiro OzakiMatthew NealonJay NeitzRobert F MullinsGregory S HagemanLincoln V Johnson
- Resource Type
- Journal article
- Publication Details
- American journal of ophthalmology, Vol.131(6), pp.767-781
- DOI
- 10.1016/S0002-9394(00)00961-2
- PMID
- 11384575
- NLM abbreviation
- Am J Ophthalmol
- ISSN
- 0002-9394
- eISSN
- 1879-1891
- Publisher
- United States
- Grant note
- EY-11527 / NEI NIH HHS EY-01931 / NEI NIH HHS EY-11515 / NEI NIH HHS EY-11521 / NEI NIH HHS
- Language
- English
- Date published
- 06/2001
- Academic Unit
- Ophthalmology and Visual Sciences
- Record Identifier
- 9983979914002771
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