Cholesterol homeostasis in the nervous system and retinal pathologies: Role of cholesterol 24S-hydroxylase (CYP46A1)

The retina is the neurosensory tissue at the posterior pole of the eye that encodes the visual transduction pathway, i.e. codes light into a nervous signal. The retina is the association of the neural retina and the retinal pigment epithelium that lays on Bruch's membrane. The physical association between these two partners and their metabolic interactions are required for the functioning of the retina, including the intake of nutrients in the retina and the maintenance of its homeostasis. Dysregulations of these equilibriums are involved in the aging processes and related diseases such as age-related macular degeneration, the leading cause of visual loss after the age of 50 years in Western populations. The retina is composed of various cell types, including glia which role is crucial for cholesterol biosynthesis in the retina. Cholesterol is the main sterol in the retina. It is mainly present as free form and as cholesteryl esters in Bruch's membrane. The extracellular accumulation of cholesteryl esters thereof is a hallmark of aging of the retina and associated to the loss of its function. Being of dietary origin and synthesized in situ, cholesterol is regulated via the interactions between retinal cells, including communications between neurons and glia and cholesterol 24S-hydroxylase (CYP46A1). Pathophysiological associations can be suggested between cholesterol homeostasis and glaucoma or age-related macular degeneration.