Cholesterol and ocular pathologies: focus on the role of cholesterol-24S-hydroxylase in cholesterol homeostasis

Abstract

-The retina is responsible for coding the light stimulus into a nervous signal that is transferred to the brain via the optic nerve. The retina is formed by the association of the neurosensory retina and the retinal pigment epithelium that is supported by Bruch's membrane. Both the physical and metabolic associations between these partners are crucial for the functioning of the retina, by means of nutrient intake and removal of the cell and metabolic debris from the retina. Dysequilibrium are involved in the aging processes and pathologies such as age-related macular degeneration, the leading cause of visual loss after the age of 50 years in Western countries. The retina is composed of several populations of cells including glia that is involved in cholesterol biosynthesis. Cholesterol is the main sterol in the retina. It is present as free form in cells and as esters in Bruch's membrane. Accumulation of cholesteryl esters has been associated with aging of the retina and impairment of the retinal function. Under dietary influence and in situ synthesized, the metabolism of cholesterol is regulated by cell interactions, including neurons and glia via cholesterol-24S-hydroxylase. Several pathophysiological associations with cholesterol and its metabolism can be suggested, especially in relation to glaucoma and age-related macular degeneration.Keywords: Retina / lipid / cholesterol / glaucoma / age-related macular degeneration / aging Résumé -Cholestérol et pathologies oculaires : focus sur le rôle de la cholestérol-24S-hydroxylase dans l'homéostasie du cholestérol. La rétine est le tissu neurosensoriel de l'oeil qui assure la transduction visuelle, c'est-à-dire le codage de l'information lumineuse en influx nerveux. Le terme de rétine regroupe l'association de la rétine neurale et de l'épithélium pigmentaire rétinien qui repose sur la membrane de Bruch. L'association physique de ces deux partenaires et leurs interactions métaboliques sont des éléments indispensables au bon fonctionnement de la rétine, à la fois en termes d'apport en nutriments et de maintien de l'homéostasie. Des dérèglements de ces équilibres sont associés au vieillissement et à des pathologies comme la dégénérescence maculaire liée à l'âge, première cause de malvoyance après 50 ans dans les populations occidentales. La rétine neurale est composée de plusieurs types cellulaires, incluant la glie dont le rôle est crucial pour la biosynthèse du cholestérol dans la rétine. Le cholestérol est le principal stérol de la rétine. Il y est présent dans la cellule essentiellement en tant que cholestérol libre et d'esters de cholestérol au niveau extracellulaire dans la membrane de Bruch. L'accumulation de ces esters de cholestérol à ce niveau est un marqueur du vieillissement de la rétine et de la diminution de sa fonction. Sous influence alimentaire et synthétisé localement, le cholestérol est également régulé via les interactions entre populations cellulaires de la rétine, comme entre neurones et glie, via la cholestérol-24S-hydroxylase. Plusieur...

Neuroprotective Effects of Low-Dose Statins in the Retinal Ultrastructure of Hypercholesterolemic Rabbits

“…In accordance with a previous study [ 16 ], we found here that, in hypercholesterolemic rabbits, RPE cells showed intracellular droplets of lipids. These lipid accumulations may occur because RPE expresses a variety of lipoprotein-specific receptors (LDLR, SR-BI, SR-BII) and scavenger receptors (CD36) that enable the recognition of circulating lipoproteins by RPE and delivery to the retina [ 1 , 10 ]. The accumulation of lipids between the inner collagenous layer and the basal lamina of the BM (as seen in many older human eyes) participates in creating a physical barrier, called the lipid wall, which may limit the exchanges between the choriocapillaris and the RPE [ 10 , 62 , 63 ].…”

“…A major consequence of the astroglial decrease (observed as a reduction of AANFB-RA and PVA-RA) in G1 could be related to the fact that these cells are an active partner of neurons by maintaining cholesterol synthesis and removal [ 1 ]. In the retina, Müller cells and astrocytes participate in the metabolism (supplying heterogeneous lipoprotein particles and ApoE) and transport of cholesterol, an essential source of lipids for the maintenance of the neuronal cell membranes [ 17 , 66 , 69 , 97 ], making neurons susceptible to alteration in long-term hypercholesterolemia.…”

“…Hypercholesterolemia constitutes an ischemic and inflammatory risk factor in certain neurodegenerative diseases [ 1 ]. Cholesterol, the main sterol in the retina, is widely distributed in all cell layers of the neuroretina, including the ganglion-cell layer and the nerve-fiber layer.…”

“…Under dietary influence and in situ synthesis, cholesterol metabolism is regulated by cell interactions, including neurons and glial cells. Glia is an active partner of neurons, maintaining cholesterol synthesis and removal [ 1 ]. Glial-derived cholesterol has been implicated as an important source of neuronal cholesterol, particularly for making new synaptic membranes [ 4 ].…”

“…Glial-derived cholesterol has been implicated as an important source of neuronal cholesterol, particularly for making new synaptic membranes [ 4 ]. Dysregulation of cholesterol in the retina has been associated with retinal impairment, reflecting the key role of this sterol in neurons [ 1 ]. Cellular cholesterol deficiency and accumulation, hallmarks of some neurodegenerative diseases involving the retina [ 5 , 6 ], highlight the importance of maintaining cholesterol homeostasis in neurons.…”