Centre des Sciences du Goût et de l'Alimentation, UMR 1324 INRA, 6265 CNRS, University of Burgundy, Centre de recherche INRA, Dijon, France.
Chem Phys Lipids. 2011 Sep;164(6):496-9. doi: 10.1016/j.chemphyslip.2011.04.006. Epub 2011 Apr 21.
Free cholesterol is the predominant form of cholesterol in the neural retina. The vertebrate neural retina exhibits its own capacity to synthesize cholesterol and meets its demand also by taking it from the circulation. Defects in cholesterol synthesis and trafficking in the neural retina has detrimental consequences on its structure and function, highlighting the crucial importance of maintaining cholesterol homeostasis in the retina. Our purpose was to give a review on the functioning of the retina, the role of cholesterol and cholesterol metabolism therein, with special emphasis on cholesterol-24S-hydroxylase (CYP46A1). Similar to the brain, the retina expresses cholesterol-24S-hydroxylase (CYP46A1) and is enriched in its metabolic product, 24S-hydroxycholesterol. We recently published that one single nucleotide polymorphism in CYP46A1 gene, designated as rs754203, was a risk factor for glaucoma. Glaucoma is the second leading cause of blindness worldwide, affecting more than 60 million people. Glaucoma is characterized by the loss of retinal ganglion cells, which show high CYP46A1 expression. These data suggest the potential involvement of CYP46A1 and 24S-hydroxycholesterol in the pathophysiology of glaucoma.
游离胆固醇是神经视网膜中胆固醇的主要形式。脊椎动物的神经视网膜表现出自身合成胆固醇的能力，也可以通过从循环中摄取胆固醇来满足其需求。胆固醇在神经视网膜中的合成和运输缺陷对其结构和功能有不利影响，这凸显了维持视网膜中胆固醇平衡的至关重要性。我们的目的是综述视网膜的功能、胆固醇及其代谢产物在其中的作用，特别强调胆固醇-24S-羟化酶（CYP46A1）。与大脑类似，视网膜表达胆固醇-24S-羟化酶（CYP46A1），并富含其代谢产物 24S-羟胆固醇。我们最近发表的研究表明，CYP46A1 基因中的一个单核苷酸多态性，称为 rs754203，是青光眼的一个风险因素。青光眼是全球第二大致盲原因，影响着超过 6000 万人。青光眼的特征是视网膜神经节细胞的丧失，这些细胞表现出高 CYP46A1 表达。这些数据表明 CYP46A1 和 24S-羟胆固醇可能参与了青光眼的病理生理学过程。
