Cholesterol-24S-hydroxylase (CYP46A1) is specifically expressed in neurons of the neural retina
Current Eye Research. 2007-01-01; 32(4): 361-366
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1. Curr Eye Res. 2007 Apr;32(4):361-6.
Cholesterol-24S-hydroxylase (CYP46A1) is specifically expressed in neurons of the
Bretillon L(1), Diczfalusy U, Björkhem I, Maire MA, Martine L, Joffre C, Acar N,
Bron A, Creuzot-Garcher C.
(1)Eye and Nutrition Research Group, UMR 1129 FLAVIC, INRA, ENESAD, University of
Burgundy, Dijon, France, and Department of Laboratory Medicine, Karolinska
University Hospital Huddinge, Stockholm, Sweden.
Increasing biological findings argue for the importance of
cholesterol-24S-hydroxylase (CYP46A1) in cholesterol homeostasis in cerebral
structures. Based on the similarity between the brain and the neural retina, the
aim of the current study was to evaluate the expression of CYP46A1 in the
mammalian retina. RT-PCR analysis of CYP46A1 in bovine samples revealed the
highest expression in the neural retina. The retinal pigment epithelium expressed
CYP46A1 gene at a low level while the ciliary body showed no expression.
Immunohistochemical evaluation of the posterior pole of rat retina showed that
the protein is specifically expressed in neurons, whereas cone-rods
photoreceptors were negative for CYP46A1 staining. The metabolite produced by
CYP46A1, 24S-hydroxycholesterol, was almost exclusively found in neural retina,
the concentration therein being more than 10-fold higher than in the retinal
pigment epithelium or the ciliary body. The results of the current study are
consistent with our primary hypothesis: the neural retina specifically expresses
cholesterol-24S-hydroxylase, a metabolizing enzyme responsible for the removal of
cholesterol in neurons. Based on the link between cholesterol-24S-hydroxylase,
24S-hydroxycholesterol, and neurologic disorders, CYP46A1 may be a valuable gene
candidate for retinal pathologies like age-related macular degeneration or
glaucomas, and 24S-hydroxycholesterol may be involved in the onset of the
degenerative processes in these diseases.
PMID: 17453958 [Indexed for MEDLINE]