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Selective Delivery of Xanthophylls to Human Retinal Pigment Epithelial Cells (ARPE‐19) via Human Lipoproteins

Age‐related macular degeneration (AMD) is an incurable disease affecting older adults in the United States that leads to blindness. Xanthophylls are dietary carotenoids of interest because they selectively accumulate in the macula of the eye and are thought to provide protection against AMD. To reach the macula, xanthophylls and other nutrients such as β‐carotene must cross the retinal pigment epithelium (RPE) through the choroid from the human blood. Xanthophylls associate mostly with HDL (high density lipoprotein) in human serum while β‐carotene associates mostly with LDL (low density lipoprotein). HDL binds to cells via a scavenger receptor class B1 (SRB1)‐dependent mechanism while LDL binds via the LDL receptor (LDLR). Using an in‐vitro, human cell model (ARPE‐19), we studied the mechanisms of xanthophyll (lutein and zeaxanthin) uptake into the RPE cell by evaluating kinetics of cell uptake when carotenoids were delivered in LDL or HDL. For lutein and β‐carotene, LDL delivery resulted in the highest rate and extent of uptake. In contrast, HDL was more effective in delivering zeaxanthin resulting in the highest rate and extent of uptake of the 3 compounds. The preferential uptake of zeaxanthin from HDL and lutein from LDL may be facilitated by SRB1 and LDLR, respectively. Adding increasing amounts of unenriched LDL to lutein‐enriched LDL and unenriched HDL to zeaxanthin‐enriched HDL, decreased xanthophyll uptake in both instances. Competition for access to SRB1 or LDLR between the xanthophyll‐enriched lipoprotein and the unenriched lipoprotein may occur as the unenriched lipoprotein concentration increases. Because carotenoid uptake is lipoprotein‐dependent, we evaluated whether competition may occur between β‐carotene, lutein, or zeaxanthin for cell uptake. Using whole serum to deliver lutein or zeaxanthin in the presence of increasing amounts of β‐carotene, lutein, or zeaxanthin, we found that β‐carotene decreased lutein uptake. Zeaxanthin uptake was unaffected by either lutein or β‐carotene. Using serum amyloid albumin (SAA), an acute phase inflammatory protein known to block HDL binding to SRB1, and BLT‐1, a chemical inhibitor of HDL uptake by SRB1, we evaluated zeaxanthin uptake by HDL in ARPE‐19 cells. Compared to the control treatment, zeaxanthin delivery via HDL was reduced by 49% and 52% by SAA and BLT, respectively. Our results suggest a selective HDL‐mediated uptake of zeaxanthin via SRB1 and potentially a LDL‐mediated uptake mechanism for lutein via LDLR. Overall, our results may partly explain selective uptake of xanthophylls into the RPE.