Expression of reverse cholesterol transport proteins ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI) in the retina and retinal pigment epithelium

Abstract

Aims Excessive lipid accumulation in Bruch’s membrane (BrM) is a hallmark of ageing, the major risk factor for age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells may utilise reverse cholesterol transport (RCT) activity to move lipid into BrM, mediated through ATP-binding cassette A1 (ABCA1) and scavenger receptor BI (SR-BI). Methods ABCA1 expression was assessed by reverse transcription polymerase chain reaction (RT-PCR) and western blotting of human RPE cell extracts. Lipid transport assays were performed using radiolabelled photoreceptor outer segments (POS). ABCA1 and SR-BI expression was examined in normal mouse eyes by immunofluorescence staining. BrMs of ABCA1 and SR-BI heterozygous mice were examined microscopically. Results Human RPE cells expressed ABCA1 mRNA and protein. The ABCA1 and SR-BI inhibitor glyburide (also known as glibenclamide) abolished basal transport of POS-derived lipids in RPE cells in the presence of high-density lipoprotein. Mouse retina and RPE expressed ABCA1 and SR-BI. SR-BI was highly expressed in RPE. BrMs were significantly thickened in SR-BI heterozygous mice, but not in ABCA1 heterozygous mice. Conclusion RPE cells express ABCA1 and SR-BI. This implies a significant role for SR-BI and ABCA1 in lipid transport and RCT in the retina and RPE.

ABCA1 rs1883025 Polymorphism Shows No Association with Neovascular Age-Related Macular Degeneration or Polypoidal Choroidal Vasculopathy in a Northern Chinese Population

“…ABCA1 mediates the efflux of cholesterol and phospholipids to lipid-poor apolipoproteins, which then form nascent HDL [27,28]. In a recent study, ABCA1 was shown to be expressed in the retina and retinal pigment epithelium [29]. Several studies have demonstrated an association between rs1883025 variants in ABCA1 and different stages of AMD in multiethnic populations.…”

The ins and outs of cholesterol in the vertebrate retina

“…Although there are some differences between SR-BI and SR-BII, both proteins have been localized to the retinal ganglion cells and Müller cells as well as to photoreceptors ( 50,55 ). ApoA1 and ABCA1 were both detected in retinal ganglion cells and the outer plexiform layer ( 50,56 ). ApoA1 immunoreactivity was also observed to be associated with photoreceptor outer segments (most likely present in the inter-photoreceptor matrix (IPM), the extracellular matrix fi lls the subretinal space) and the inner segment of rods, but not cones, as well as with the apical face of RPE cells ( 50 ).…”

“…This close anatomical association between the RPE and photoreceptors is one of the factors that promotes the ability of the RPE to, on the one hand, provide nutrients and oxygen to the photoreceptor cells and, on the other hand, eliminate metabolic wastes generated by the neural retina, including those resulting from the shedding of outer segments tips and their subsequent phagocytosis and degradation by the RPE. The RPE cells express a variety of lipoprotein-specifi c and scavenger receptors: VLDL receptor ( 47 ), LDL receptor (LDL-R) ( 12,48,49 ), and the so-called scavenger receptors CD36 ( 48,(50)(51)(52)(53)(54), SR-BI, and BII ( 50,52,55,56 ). Interestingly, LDL-R was also localized to the endothelial cells of the choriocapillaris, the photoreceptor inner segments, retinal ganglion cells, and Müller cells ( 12 ).…”

Pathways of cholesterol homeostasis in mouse retina responsive to dietary and pharmacologic treatments

“…Thus, most of the studied genes seem to be expressed as proteins in the retina. Mouse retina can now be compared with human retina ( 11 ), the retina of other species ( 10,14 ), and immunohistochemistry characterizations by others ( 35 ). Quantitative methodologies should be used to confi rm immunolocalizations.…”