Scavenger Receptor SR–BI Is Involved in Selective Uptake of Xanthophylls in the Retina

Abstract

Abstract: : Purpose: The aim of this study was to test a hypothesized role of a scavenger receptor SR–BI, which is responsible for selective uptake of cholesterol esters and α–tocopherol and is expressed throughout the retina, in the uptake of xanthophylls by the retinal pigment epithelium (RPE). Methods: Confluent ARPE–19 cells in culture were fed every 2 to 3 days for up to three weeks with 2 µM zeaxanthin and/or 35 µM cholesterol solubilized in culture medium supplemented with 0.2% tetrahydrofuran and 10% of fetal calf serum. Exposure of cells to cholesterol was used to increase the expression of SR–BI and to determine whether or not cholesterol affects the uptake of zeaxanthin. Zeaxanthin uptake was monitored by spectrophometry in cell extracts. SDS–PAGE separation of proteins followed by Western blotting were used to quantify the expression of SR–BI. Results: Feeding cells with zeaxanthin resulted in a monotonic increase of concentration of cellular zeaxanthin that reached about 165 pmol/million cells after 3 weeks of feeding. Cholesterol accelerated the uptake of zeaxanthin possibly due to upregulation of SR–BI expression. Zeaxanthin alone induced over a 20–fold increased expression of SR–BI compared to control ARPE–19 cells cultured in the absence of zeaxanthin and cholesterol. Conclusions:Increased expression of SR–BI upon exposure of RPE cells to zeaxanthin and the stimulatory effect of cholesterol on zeaxanthin uptake suggest that SR–BI is involved in the uptake of xanthophylls. Further studies are needed to elucidate the exact mechanism of xanthophyll uptake, whose dysfunction may lead to a decreased content of macular pigment observed in the elderly patients with lower visual sensitivity or suffering from age–related macular degeneration.

Keywords: macular pigment • retinal pigment epithelium • age-related macular degeneration