The purpose of this study was to investigate the mechanisms by which carotenoids [xanthophylls vs. bcarotene (b-C)] are taken up by retinal pigment epithelial (RPE) cells. The human RPE cell line, ARPE-19, was used. When ARPE-19 cells were fully differentiated (7-9 weeks), the xanthophylls lutein (LUT) and zeaxanthin (ZEA) were taken up by cells to an extent 2-fold higher than b-C (P , 0.05). At 9 weeks, cellular uptakes were 1.6, 2.5, and 3.2%, respectively, for b-C, LUT, and ZEA. Similar extents were observed when carotenoids were delivered in either Tween 40 or "chylomicrons" produced by Caco-2 cells. Differentiated ARPE-19 cells did not exhibit any detectable b-C 15,15′-oxygenase activity or convert exogenous b-C into vitamin A. When using specific antibodies against the lipid transporters cluster determinant 36 (CD36) and scavenger receptor class B type I (SR-BI), cellular uptake of b-C and ZEA were significantly decreased (40-60%) with anti-SR-BI but not with anti-CD36. Small interfering RNA transfection for SR-BI led to marked knockdown of SR-BI protein expression (?90%), which resulted in decreased b-C and ZEA uptakes by 51% and 87%, respectively. Thus, the present data show that RPE cells preferentially take up xanthophylls versus the carotene by a process that appears to be entirely SR-BI-dependent for ZEA and partly so for b-C. This mechanism may explain, in part, the preferential accumulation of xanthophylls in the macula of the retina.-During, A., S. Doraiswamy, and E. H. Harrison. Xanthophylls are preferentially taken up compared with b-carotene by retinal cells via a SRBI-dependent mechanism.

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