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We investigated the capacity of Royal College of Surgeons (RCS) rat retinal pigment epithelial (RPE) cells to take up all-trans-retinol (ROL) (vitamin A) and to metabolize it into retinyl esters (RE). Cultures of RPE cells were established from RCS and control newborn rats. All-trans-ROL was delivered to the apical surface of the RPE monolayer. Retinoids were analyzed by high-performance liquid chromatography. The cellular retinol-binding protein type I (CRBP-I) was assessed by Western blotting. Before supplementation with ROL, RE were lower in RCS rats. After ROL supplementation, esters increased and reached values that were similar in the two strains, but the increase, expressed relative to the initial value, was higher in RCS rats. The uptake of ROL and the level of CRBP-I were greater in RCS rats. Our results provide evidence of a functional retinol esterifying enzyme in cultured RCS RPE cells and suggest that CRBP-I could play a role in the uptake and esterification of ROL in the RPE cells. [Copyright &y& Elsevier]

Dry age-related macular degeneration and Stargardt disease undergo a known toxic mechanism caused by carbonyl and oxidative stresses (COS). This is responsible for accumulation in the retinal pigment epithelium (RPE) of A2E, a main toxic pyridinium bis -retinoid lipofuscin component. Previous studies have shown that carbonyl stress in retinal cells could be reduced by an alkyl-phloroglucinol-DHA conjugate (lipophenol). Here, we performed a rational design of different families of lipophenols to conserve anti-carbonyl stress activities and improve antioxidant properties. Five synthetic pathways leading to alkyl-(poly)phenol derivatives, with phloroglucinol, resveratrol, catechin and quercetin as the main backbone, linked to poly-unsaturated fatty acid, are presented. These lipophenols were evaluated in ARPE-19 cell line for their anti-COS properties and a structure-activity relationship study is proposed. Protection of ARPE-19 cells against A2E toxicity was assessed for the four best candidates. Finally, interesting anti-COS properties of the most promising quercetin lipophenol were confirmed in primary RPE cells. Image 1 • Carbonyl and oxidative stresses play a crucial role in macular degeneration. • All- trans -retinal accumulates abnormally in AMD causing toxic A2E formation. • Lipophenol derivatives are polyphenols functionalized with PUFA. • Quercetin lipophenol is a potent photo-oxidative toxicity suppressor in RPE cells. • Lipophenols protect against toxicity induced by carbonyl and oxidative stresses. [ABSTRACT FROM AUTHOR]