Cholesterol homeostasis in the vertebrate retina: biology and pathobiology

Abstract

Cholesterol is a quantitatively and biologically significant constituent of all mammalian cell membrane, including those that comprise the retina. Retinal cholesterol homeostasis entails the interplay between de novo synthesis, uptake, intra-retinal sterol transport, metabolism and efflux. Defects in these complex processes are associated with several congenital and age-related disorders of the visual system. Herein, we provide an overview of the following topics: a) cholesterol synthesis in the neural retina; b) lipoprotein uptake and intraretinal sterol transport in the neural retina and the retinal pigment epithelium (RPE); c) cholesterol efflux from the neural retina and the RPE; and d) biology and pathobiology of defects in sterol synthesis and sterol oxidation in the neural retina and the RPE. We focus, in particular, on studies involving animal models of monogenic disorders pertinent to the above topics, as well as in vitro models using biochemical, metabolic, and omic approaches. We also identify current knowledge gaps as well as opportunities in the field that beg further research in this topic area.

Renal function and lipid metabolism are major predictors of circumpapillary retinal nerve fiber layer thickness—the LIFE-Adult Study

“…Pathophysiologically, the retina is capable of the rapid uptake of distinct cholesterol particles from the circulation [ 27 ]. Furthermore, many relevant proteins and receptors necessary for uptake, transport, metabolism, synthesis, and efflux of cholesterol and other lipid molecules [ 28 ] are expressed in cells of the human RNFL (i.e., ganglion cells and glia cell types such as astrocytes and Müller cells) [ 29 , 30 ]. Moreover, lipid-lowering drugs, for instance, statins, are permeable to the blood-retinal barrier [ 31 ], and chronic (i.e., for 6 weeks) simvastatin treatment in mice decreases total retinal cholesterol content by 24% [ 31 ].…”

Lipid metabolism dysregulation in diabetic retinopathy

“…3 ) ( 74 ). A more detailed overview of cholesterol homeostasis in the vertebrate retina is provided by Rao and Fliesler in this issue ( 75 ). Unique metabolic demands and the highly specialized structure and function of the retina dictate complex regulatory pathways to support retinal metabolism while preserving autonomy behind the two blood-retinal barriers (BRBs) that separate it from the systemic circulation ( 76 , 77 , 78 ).…”

The possible alleviating effect of garlic supplement on the neural retina in a rat model of hypercholesterolemia: a histological and immunohistochemical study

“…Cholesterol transport is vital as it supplies retinal neurons with the lipids required for the preservation and restoration of their cell membranes. 4 Interestingly, the retinal pigmented epithelium, and probably Muller cells of the retina, contain low density lipoprotein (LDL) receptors that can uptake circulating LDL. The regulation of cholesterol metabolism is accomplished via neuronal and glial cell interaction.…”