期刊
JOURNAL OF LIPID RESEARCH
卷 56, 期 1, 页码 81-97出版社
ELSEVIER
DOI: 10.1194/jlr.M053439
关键词
cytochrome P450; transcriptional regulation; posttranslational regulation; 3-hydroxy-3-methyl-glutaryl-CoA reductase; liver X receptor; sterol-regulatory element binding protein; RPE65; age-related macular degeneration
资金
- National Institutes of Health [EY018383, EY11373]
- Ohio Lions Eye Research Foundation
- Research to Prevent Blindness
- Jules and Doris Stein Professorship from the Research to Prevent Blindness Foundation
- NATIONAL EYE INSTITUTE [P30EY011373, R01EY018383] Funding Source: NIH RePORTER
Effects of serum cholesterol on cholesterol content in the retina are currently unknown. It is also unclear how cholesterol levels are controlled in the retina. High-cholesterol diet and oral administrations of simvastatin were used to modulate serum cholesterol in mice. These treatments only modestly affected cholesterol content in the retina and had no significant effect on retinal expression of the major cholesterol-and vision-related genes; the sterol-regulatory element binding protein pathway of transcriptional regulation does not seem to be operative in the retina under the experimental conditions used. Evidence is obtained that posttranslational mechanisms play a role in the control of retinal cholesterol. Retinal genes were only up-regulated by oral administrations of TO901317 activating liver X receptors. Three of the upregulated genes could be of particular importance (apoD, Idol, and Rpe65) and have not yet been considered in the context of cholesterol homeostasis in the retina. Collectively, the data obtained identify specific features of retinal cholesterol maintenance and suggest additional therapies for age-related macular degeneration, a blinding disease characterized by cholesterol and lipid accumulations in chorioretinal tissues.
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