Mechanisms of Transport and Delivery of Vitamin A and Carotenoids to the Retinal Pigment Epithelium.

Abstract

Vision depends on the delivery of vitamin A (retinol) to the retina. Retinol in blood is bound to retinol-binding protein (RBP). Retinal pigment epithelia (RPE) cells express the RBP receptor, STRA6, that facilitates uptake of retinol. The retinol is then converted to retinyl esters by the enzyme lecithin:retinol acyltransferase. The esters are the substrate for RPE65, an enzyme that produces 11-cis retinol, which is converted to 11-cis retinaldehyde for transport to the photoreceptors to form rhodopsin. The dietary xanthophylls, lutein (LUT) and zeaxanthin (ZEA), accumulate in the macula of the eye, providing protection against age-related macular degeneration. To reach the macula, carotenoids cross the RPE. In blood, xanthophylls and β-carotene mostly associate with high-density lipoprotein (HDL) and low-density lipoprotein (LDL), respectively. Studies using a human RPE cell model evaluate the kinetics of cell uptake when carotenoids are delivered in LDL or HDL. For LUT and β-carotene, LDL delivery result in the highest rate of uptake. HDL is more effective in delivering ZEA (and meso-ZEA). This selective HDL-mediated uptake of ZEA, via a scavenger receptor and LDL-mediated uptake of LUT and β-carotene provides a mechanism for the selective accumulation of ZEA > LUT and xanthophylls over β-carotene in the macula.