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Preejith P Vachali, Binxing Li, Aruna Gorusupudi, Zhengqing Shen, Brian Besch, Kelly Nelson, Paul S Bernstein; Optimization of Retinal Uptake of Lutein and Zeaxanthin in Transgenic Mice. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3486.
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The macular pigment carotenoids, lutein and zeaxanthin, exhibit low systemic and undetectable ocular bioavailability in wild-type (WT) mice. Recent studies from our laboratory suggest that this is due to the active carotenoid cleavage enzymes (BCO1 and BCO2) present in these WT mice. Here we report the reproducible delivery of both lutein and zeaxanthin in BCO double knockout mice.
BCO1-/- / BCO2 -/- double KO mice (BCODKO) and WT mice (8-12 weeks) were used for this study. The mice were put on a vitamin-A deficient chow for 4 weeks, and after that the experimental groups (20-25 each) received zeaxanthin or lutein in DSM ActiLease beadlet chow (1g/kg) for another 4 weeks. The tissues were harvested after 4 weeks of feeding, and the samples were analyzed using HPLC.
The zeaxanthin levels in the liver samples of BCODKO and WT were 6584 ± 2179 and 5686 ± 1884 ng/g respectively. The serum zeaxanthin levels for BCODKO and WT were 1332 ± 435 and 925 ± 243 ng/ml respectively. The zeaxanthin levels in BCODKO RPE/choroid and retina were 4.73 ± 0.61 ng/pair and 1.16 ± 0.15 ng/pair respectively. The WT RPE/choroid had 0.94 ± 0.30 ng/pair zeaxanthin, and no zeaxanthin was detected in WT retina. The lutein levels in the liver samples of BCODKO and WT were 7242 ± 1571and 4792 ± 839 ng/g respectively. The serum lutein levels for BCODKO and WT were 1107 ± 295 and 394 ± 107 ng/ml respectively. Lutein level in BCODKO RPE/choroid and retina were 2.97 ± 0.45 ng/pair and 0.75 ± 0.19 ng/pair respectively. In the WT, RPE/choroid had 0.45 ± 0.10 ng/pair lutein and no lutein was detected in WT retina. There were no carotenoids present in the WT lens, whereas BCODKO lens had trace amounts (Lower than Quantitation).
In BCODKO mice, we could detect both lutein and zeaxanthin in the retina. The results were statistically significant compared with the wild type mice. Studies in progress using BCO1-/- or BCO2 -/- single knockout mice suggest that the double knockout has a higher relative uptake of carotenoids into the retina. These results emphasize the importance of using transgenic mice lacking carotenoid cleavage enzymes for the successful retinal delivery of macular pigments when studying the ocular effects of lutein and zeaxanthin in mouse models of retinal disease.
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