J. Lipid Res.
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A more recent version of this article appeared on February 1, 2004

Papers In Press, published online ahead of print November 1, 2003
J. Lipid Res., doi:10.1194/jlr.M300306-JLR200
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Submitted on July 9, 2003
Revised on September 17, 2003
Accepted on October 24, 2003

Regulated expression of apolipoprotein E by human retinal pigment epithelial cells

Brian Y. Ishida, Kathy R. Bailey, Keith G. Duncan, Robert J. Chalkley, A. L. Burlingame, John P. Kane, and Daniel M. Schwartz

Cardiovascular Research Institute, University of California, San Francisco, San Francisco, CA 94143-0130

Corresponding Author: ishida{at}itsa.ucsf.edu

In early age-related macular degeneration (AMD) lipid containing deposits (drusen) accumulate in Bruch’s membrane underlying the retinal pigment epithelium (RPE). Recent studies indicate that apolipoprotein E (apoE) may play a role in lipid trafficking in AMD. When compared to the apoE3 allele, the apoE4 and apoE2 alleles are associated with decreased and increased risk for AMD, respectively, drusen contain high levels of apoE, and apoE null mice develop lipid deposits in Bruch’s membrane similar to those observed in AMD. Primary cultures of human RPE cells expressing the apoE3 allele were grown on Transwell® culture plates. Western blotting, ELISA assay, and mass spectrometry confirmed that apoE3 was secreted into the apical and basal chambers and that secretion was up regulated by thyroid hormone (T3), 9-cis retinoic acid (RA) and 22(R)-hydroxycholesterol (HC). In addition, basally secreted apoE associated with exogenously added HDL. The results indicate that apoE secretion can be regulated by specific hormones and that apoE associates with HDL. The findings are consistent with a role for apoE in lipid trafficking through Bruch’s membrane and may be relevant to AMD.


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