Background/aims: Excessive lipid accumulation in Bruch's membrane (BrM) is a hallmark of aging, the major risk factor for age-related macular degeneration (AMD). Excessive lipid accumulation in Bruch's membrane (BrM), thought to originate from photoreceptor outer segments (POS), is a hallmark of early age-related macular degeneration (AMD). Retinal pigment epithelial (RPE) cells may utilize 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 radiolabeled 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 abolished basal transport of POS-derived lipids in RPE cells in the presence of HDL. Mouse retina and RPE expressed ABCA1 and SR-BI. SR-BI was highly expressed mainly in RPE. BrMs were significantly significantly thickened in SR-BI heterozygous mice, but not ABCA1, heterozygous mice.
Conclusion: RPE cells express ABCA1 and SR-BI. The results imply a significant role for SR-BI and ABCA1 in lipid transport and RCT in the retina and RPE.
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