Journal
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Volume 52, Issue 1, Pages 594-603Publisher
ASSOC RESEARCH VISION OPHTHALMOLOGY INC
DOI: 10.1167/iovs.10-6021
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Funding
- National Institutes of Health [EY018383, AG024336]
- Swedish Science Council, Brain Power
- National Eye Institute
- Visual Sciences Training Program [T32 EY07157]
- Research to Prevent Blindness Foundation
- NATIONAL EYE INSTITUTE [T32EY007157, R01EY018383] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE ON AGING [K02AG024336] Funding Source: NIH RePORTER
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PURPOSE. Accumulating evidence indicates a link between cholesterol and age-related macular degeneration. Yet, little is known about cholesterol elimination from the retina and retinal pigment epithelium (RPE), the two layers that are damaged in this blinding disease. Several different pathways of enzymatic cholesterol removal exist in extraocular tissues. The authors tested whether metabolites from these pathways could also be quantified in the bovine and human retina and RPE. For comparison, they measured cholesterol oxidation products in two regions of the bovine and human brain and in the bovine liver and adrenal glands. METHODS. Sterol quantification was carried out by isotope dilution gas chromatography-mass spectrometry. Bovine tissues were used first to optimize analytical procedures and to investigate postmortem changes in oxysterol concentrations. Then human specimens were analyzed for oxysterol concentrations. RESULTS. Qualitatively, oxysterol profiles were similar in the bovine and human tissues. In the human retina and RPE, the authors could not detect 27-hydroxycholesterol but unexpectedly found that its oxidation product, 5-cholestenoic acid, is the most abundant oxysterol, varying up to threefold in different persons. 24S-Hydroxysterol and pregnenolone were also present in the retina, but at much lower quantities and without significant interindividual variability. In the brain, the predominant oxysterol was 24S-hydroxycholesterol. CONCLUSIONS. The oxysterol profile of the retina suggests that all known pathways of cholesterol elimination in extraocular organs are operative in the retina and that they likely vary depending on specific cell type. However, overall oxidation to 5-cholestenoic acid appears to be the predominant mechanism for cholesterol elimination from this organ. ( Invest Ophthalmol Vis Sci. 2011;52:594-603) DOI:10.1167/iovs.10-6021
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