Regulated expression of apolipoprotein E by human retinal pigment epithelial cells

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. Compared with the apoE3 allele, t...

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Bibliographic Details
Published in:Journal of lipid research 2004-02, Vol.45 (2), p.263-271
Main Authors: Ishida, Brian Y., Bailey, Kathy R., Duncan, Keith G., Chalkley, Robert J., Burlingame, A.L., Kane, John P., Schwartz, Daniel M.
Format: Article
Language:English
Subjects:
Adult
age-related macular degeneration
Alleles
Amino Acid Sequence
Apolipoproteins E - biosynthesis
Apolipoproteins E - genetics
Biological Transport - physiology
Bruch Membrane - metabolism
Bruch's membrane
Cells, Cultured
high density lipoprotein
Humans
Hydroxycholesterols
Lipid Metabolism
Lipoproteins, HDL - metabolism
Macular Degeneration - metabolism
Male
Molecular Sequence Data
Pigment Epithelium of Eye - metabolism
Polymorphism, Genetic
retina
Retinal Pigments - metabolism
thyroid hormone
Tretinoin - metabolism
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Summary: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. Compared with 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 upregulated by thyroid hormone, 9-cis-retinoic acid, and 22(R)-hydroxycholesterol. In addition, basally secreted apoE associated with exogenously added HDL. These 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.
ISSN:0022-2275
1539-7262
DOI:10.1194/jlr.M300306-JLR200