title: Mechanisms of selective delivery of xanthophylls to retinal pigment epithelial cells by human lipoproteins.
abstract: The xanthophylls, lutein and zeaxanthin, are dietary carotenoids that selectively accumulate in the macula of the eye providing protection against age-related macular degeneration. To reach the macula, carotenoids cross the retinal pigment epithelium (RPE). Xanthophylls and β-carotene mostly associate with HDL and LDL, respectively. HDL binds to cells via a scavenger receptor class B1 (SR-B1)-dependent mechanism, while LDL binds via the LDL receptor. Using an in-vitro, human RPE cell model (ARPE-19), we studied the mechanisms of carotenoid uptake into the RPE by evaluating kinetics of cell uptake when delivered in serum or isolated LDL or HDL. For lutein and β-carotene, LDL delivery resulted in the highest rates and extents of uptake. In contrast, HDL was more effective in delivering zeaxanthin and meso-zeaxanthin leading to the highest rates and extents of uptake of all four carotenoids. Inhibitors of SR-B1 suppressed zeaxanthin delivery via HDL. Results show a selective HDL-mediated uptake of zeaxanthin and meso-zeaxanthin via SR-B1 and a LDL-mediated uptake of lutein. This demonstrates a plausible mechanism for the selective accumulation of zeaxanthin greater than lutein and xanthophylls over β-carotene in the retina. We found no evidence of xanthophyll metabolism to apocarotenoids or lutein conversion to meso-zeaxanthin.
authors.affiliation: Department of Human Sciences, The Ohio State University, Columbus, OH 43210.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Thomas
authors.affiliation: Department of Human Sciences, The Ohio State University, Columbus, OH 43210. Electronic address: Harrison.304@osu.edu.
authors.forename: Earl H
authors.initials: EH
authors.lastname: Harrison
mesh_terms: D001693:Biological Transport, Active / Q000502:physiology; D002460:Cell Line; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008077:Lipoproteins, LDL / Q000378:metabolism*; D014975:Lutein / Q000378:metabolism*; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000378:metabolism*; D051122:Scavenger Receptors, Class B / Q000378:metabolism*; D065146:Zeaxanthins / Q000378:metabolism*; D019207:beta Carotene / Q000378:metabolism
chemical_list: D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; C495124:SCARB1 protein, human; D051122:Scavenger Receptors, Class B; D065146:Zeaxanthins; D019207:beta Carotene; D014975:Lutein
keywords: carotenoids; dietary lipids; eye; high density lipoprotein; low density lipoprotein; lutein; retina; scavenger receptors; transport; zeaxanthin