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Expression of Reverse Cholesterol Transport Proteins ABCA1 and SR-BI in the Retina and RPE
  1. Keith G Duncan (kgduncan{at}pacbell.net),
  2. Kamran Hosseini,
  3. Kathy R Bailey (baileyk{at}vision.ucsf.edu),
  4. Haidong Yang (haidong.yang{at}ucsf.edu),
  5. Robert J Lowe,
  6. Michael T Matthes,
  7. John P Kane (john.kane{at}ucsf.edu),
  8. Matthew M LaVail (matthew.lavail{at}ucsf.edu),
  9. Daniel M Schwartz (schwartz7{at}mindspring.com),
  10. Jacque L Duncan (duncanj{at}vision.ucsf.edu)
  1. University of California, San Francisco, United States
  2. University of California, San Francisco, United States
  3. University of California, San Francisco, United States
  4. University of California, San Francisco, United States
  5. University of California, San Francisco, United States
  6. University of California, San Francisco, United States
  7. University of California, San Francisco, United States
  8. University of California, San Francisco, United States
  9. University of California, San Francisco, United States
  10. University of California, San Francisco, United States

    Abstract

    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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