Abstract
Purpose: :
Lutein and zeaxanthin, the principal carotenoids in human eyes, are thought to play a protective role against age-related macular degeneration and cataract. A number of recent studies have examined carotenoid effects in various mouse models of eye disease, but no study has convincingly demonstrated that carotenoids actually accumulate in the mouse eye. After studying a variety of delivery forms and dosages, we have developed a method for reliable uptake of carotenoids into mouse eyes.
Methods: :
A 20% emulsion of purified marigold carotenoids (92% 3R,3’R,6’R-lutein and 8% 3R,3’R-zeaxanthin) dissolved in safflower oil was obtained from Kemin Health (Des Moines, Iowa). 2g/kg of carotenoid was orally administrated daily to 2 month old C57BL/6 mice, while control mice were fed the same volume of safflower oil. Eyes, liver, and serum were harvested after 4 weeks of supplementation. All samples were extracted with tetrahydrofuran containing 0.1% BHT. Carotenoids were then analyzed by HPLC on cyano and chiral columns with diode-array and mass spectral detection.
Results: :
Control mice had barely detectable lutein and zeaxanthin in serum and liver, and none was detectable in the eye. With supplementation, we could achieve serum levels ~1/5 of normal human serum, and liver levels increased substantially. Both serum and liver had lutein:zeaxanthin ratios similar to the administered material. The lutein:zeaxanthin ratio was dramatically different in the supplemented mice with 3.50 ± 1.90 ng lutein and 6.17 ± 1.67 ng zeaxanthin detected per pair of eyes. Chiral HPLC confirmed that no 3R,3’S-meso-zeaxanthin was produced.
Conclusions: :
These results indicate that with high-dose supplementation, carotenoids can be delivered to the mouse eye. The altered lutein:zeaxanthin ratio is consistent with the essential role of specific transport and binding proteins in mediating carotenoid uptake into the mammalian eye. With further optimization of carotenoid delivery and uptake, the mouse could serve as a useful model for lutein and zeaxanthin function in the retina.
Keywords: carotenoids/carotenoid binding proteins • macula/fovea • nutritional factors