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Functional Role of Xanthophyll Metabolism Related Genes in Human Retinal Pigment Epithelial Cells
Author(s) -
Gong Xiaoming,
Marisiddaiah Raju,
Afeld Jamiee,
Wiener Doris,
Rubin Lewis P.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.975.17
Subject(s) - xanthophyll , lutein , retinal pigment epithelium , zeaxanthin , cd36 , biology , retinal , microbiology and biotechnology , macular degeneration , chemistry , carotenoid , biochemistry , receptor , medicine , ophthalmology
Xanthophyll carotenoids (lutein, zeaxanthin) preferentially accumulate in the macula of the human retina. They play a critical role in protecting the macula from oxidant and photo‐damage. Previous studies have indicated macular pigment density (xanthophyll content) is inversely related to adult onset age‐related macular degeneration (AMD). The regulation of macular pigment density in retinal pigment epithelium (RPE) is under active investigation. We determined the expression of genes related to carotenoid uptake and metabolism in human retinal pigment epithelial (ARPE‐19) cells using message (qRT‐PCR) and protein (Western blot). Xanthophyll uptake and transport were assayed using polarized ARPE cells grown to confluence. ARPE cells express scavenger receptors (SR‐B1, CD36, LDLR but not SR‐A), carotenoid cleavage enzymes (CMO1, CMO2) and transport related protein (ABCA1). RPE expresses high levels of SR‐B1, LDLR, CMO2 and ABCA1, and lower expression of CD36 and CMO1. RPE exposure to specific carotenoids (beta‐carotene, lycopene, lutein, astaxanthin) induces different expression patterns. Furthermore, gene expression profiles significantly changed when RPE cells were exposed to graded oxidative stress. Finally, we determined that lutein uptake and transport is directional across polarized ARPE monolayers: significantly higher from basolateral to apical surface than in the opposite direction. Of note, co‐incubation with beta‐carotene decreased lutein uptake and transport rates. These findings support the hypothesis that xanthophyll (especially lutein) uptake, metabolism, and transport are critical in macular pigment homeostasis. We speculate that altering RPE gene expression profiles by protective (xanthophyll) or deleterious (oxidative stress) factors point to molecular mechanisms in the pathogenesis of AMD. (NIH HD42174, Muma Family Endowment)