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Metabolism of cholesterol in health and disease of the retina
Author(s) -
BRETILLON L
Publication year - 2011
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2011.2112.x
Subject(s) - retina , cholesterol , liver x receptor , biology , oxysterol , lipoprotein , retinal , sterol , microbiology and biotechnology , chemistry , medicine , biochemistry , gene , neuroscience , nuclear receptor , transcription factor
Abstract Purpose Cholesterol is the main sterol in the vertebrate retina. Methods Deposits of free cholesterol and cholesteryl esters at the basement of RPE are hallmarks of aging in humans, and AMD, the leading cause of vision loss in the Western world. Results Cholesterol in the neuroretina originates from in situ synthesis and extra‐retinal sources. The relative contribution of cholesterol coming from the circulation and local biosynthesis remains unknown. Tight junctions between retinal pigment epithelial (RPE) cells limit the intercellular movements of molecules to water and small molecules. RPE cells express various lipoprotein and scavenger receptors which can promote the recognition of cholesterol‐rich lipoprotein and enhance the entry of cholesterol in the neurosensory retina. Both the neurosensory retina and RPE cells express proteins which participate to cholesterol export in other tissues than the retina, including CYP46A1. CYP46A1 would represent a mechanism of cholesterol removal from neurons, by catalyzing the hydroxylation of cholesterol at position C24. Other mechanisms than CYP46A1 have been described in the retina, including formation of 7‐ketocholesterol or 27‐hydroxycholesterol. Conclusion Interestingly a single nucleotide polymorphism in cyp46a1 gene was associated with a significant risk for glaucoma, the second leading cause of blindness worldwide.