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Preejith P Vachali, Binxing Li, Aruna Gorusupudi, Zhengqing Shen, Brian M Besch, Simone Longo, Kelly Nelson, Paul S Bernstein; Retinal and RPE/Choroid Uptake of Lutein, Zeaxanthin, and β-Carotene in Mice. Invest. Ophthalmol. Vis. Sci. 2016;57(12):3617.
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Mouse models are important in studying age-related macular degeneration (AMD), including the effect of nutritional supplementation. In wild-type mice, carotenoids exhibit relatively low oral bioavailability due to the presence of active carotenoid cleavage enzymes (BCO1 and BCO2). In this study, we report the delivery of lutein, zeaxanthin, and β-carotene to the ocular tissues of BCO knockout mice.
BCO1 knockout (BCO1-/-), BCO2 knockout (BCO2-/-), BCO1/BCO2 double knockout (DK), and wild type (WT) mice (8-12 weeks) were used for this study. The experimental groups (n=20-25 per group) received lutein, zeaxanthin, and β-carotene in the form of DSM ActiLease beadlet chow (1g/kg) for 4 weeks. Control group mice received placebo chow. The tissues were harvested after 4 weeks of feeding, and the carotenoid contents were analyzed using HPLC.
WT mice never have detectable carotenoids in their retinas, even when receving high-dose supplemention, and low levels of carotenoids are typically found in the RPE/choroid of WT mice. In BCO knockout mice, we were able to detect lutein, zeaxanthin, and β-carotene in the retina. Significant promotion of carotenoid uptake into the RPE/choroid was was also observed. Compared to BCO1-/- and BCO2-/-, the retinas of DK mice had enhanced uptake of carotenoids.The results are summarized in Tables 1 and 2.Control chow mice never had detectable levels of carotenoids. There were no carotenoids present in the WT and BCO-/- lenses, whereas the DK lens had trace amounts.
Lutein and zeaxanthin exhibited better retinal uptake relative to β-carotene. Knockout of BCO1 particularly enhances uptake of β-carotene into the RPE/choroid, while knockout of BCO2 specifically promotes uptake of the xanthopylls lutein and zeaxanthin into both the retina and the RPE/choroid. These results reinforce the importance of knocking out carotenoid cleavage enzymes for the successful retinal delivery of carotenoids in mouse models of AMD.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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