Cholesterol-24S-hydroxylase (CYP46A1) is specifically expressed in neurons of the neural retina

Abstract

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.