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Binxing Li, Preejith Vachali, Zhengqing Shen, Brian Besch, Paul Bernstein; Delivery of Zeaxanthin to the Mouse Retina. Invest. Ophthalmol. Vis. Sci. 2013;54(15):1705.
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© ARVO (1962-2015); The Authors (2016-present)
The macular pigment carotenoids, zeaxanthin and lutein, may reduce the risk of age- related macular degeneration (AMD). Until now, reproducible delivery of lutein and/or zeaxanthin to the mouse retina has not been reliably demonstrated, raising questions as to the relevance of previously published mouse model studies of carotenoid effects on the rodent eye. Recent data indicate that the mouse carotenoid cleavage enzymes, BCO1 and/or BCO2, may cleave lutein and zeaxanthin. To investigate whether or not BCO1 and/or BCO2 can inhibit the delivery of macular carotenoids to the mouse retina, we studied BCO1 knockout mice (BCO1 KO), BCO2 knockout mice (BCO2 KO), and BCO1/BCO2 double knockout mice (BCO1/BCO2 KO) supplemented with zeaxanthin.
9 to 12-week-old BCO1 KO, BCO2 KO, BCO1/BCO2 KO and wild type (WT) mice were maintained on a vitamin-A deficient diet for 4 weeks before feeding them zeaxanthin. 5 mice in each genotype group were fed a DSM ActiLease zeaxanthin beadlet chow. After 4 weeks, all the mice were euthanized, and serum, liver, retina, RPE and lens were collected. Carotenoids were extracted using standard methods and analyzed by HPLC.
The internal organs of all knockout mice exhibited a distinct yellow coloration, while the WT mice remained normal in color. The zeaxanthin level in WT mouse serum was 96.8 ng/ mL, while the zeaxanthin levels in serum of BCO1 KO, BCO2 KO, and BCO1/BCO2 KO mice were significantly increased to 226.4ng/mL, 317.6 ng /mL and 189.8 ng/mL, respectively. The concentration of zeaxathin in WT mouse liver was 237.1 ng/g, while in the liver of BCO1 KO, BCO2 KO, and BCO1/BCO2 KO mice, the concentration of zeaxanthin was significantly elevated at 794.1 ng/g, 1716.6 ng/g and 1738.8ng/g, respectively. The concentrations of zeaxanthin in the RPE of WT, BCO1 KO, BCO2 KO, BCO1/BCO2 KO mice were 0.77ng/pair, 0.44ng/pair, 1.58 ng/pair and 0.45 ng/pair, respectively. The zeaxanthin levels in the retina of BCO1 KO, BCO2 KO, BCO1/BCO2 KO mice were 0.03 ng/pair, 0.44ng/pair and 0.09 ng/ pair. No zeaxanthin was detected in the retina of WT mice or in the lenses of any mice.
Our results indicate that reliable delivery of carotenoids to the retina of the mouse eye may require knock out of one or both of the known carotenoid cleavage enzymes.
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