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.
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Funding Supported by a Physician Scientist Award (JLD); Unrestricted Grant from Research to Prevent Blindness – a Career Development Award (JLD); Center Grant from the Foundation Fighting Blindness (MML, JLD); the Dennis Jahnigen Career Development Scholars Award (JLD); NIH-NEI grants EY00415 (JLD), EY01919 and EY002162 (MML); That Man May See, Inc. (MML, JLD); The Bernard A. Newcomb Macular Degeneration Fund (JLD); Hope for Vision (JLD); and the Karl Kirchgessner Foundation (JLD).
Competing interests None declared.
Ethics approval All procedures were approved by the University of California San Francisco Institutional Animal Care and Use Committee.