Abstract
Recent studies indicate that an excessive inflammatory response is etiologically related to the pathogenesis of age-related macular degeneration (AMD). Epidemiologic studies suggest that dietary lutein and zeaxanthin intake is inversely associated systemic inflammation and risk for AMD. The objective of this work is to directly determine the effects of lutein and zeaxanthin supplementation on ocular and systemic inflammatory response. ARPE-19 cells and primary murine macrophages were cultured in the presence of 0, 1 and 10 μM lutein or zeaxanthin for 1–3 days and then stimulated with lipopolysaccharide (LPS) in fresh medium for 8 h. Levels of IL-6, IL-8 and TNFα in the medium were determined by ELISA and used as indicators of inflammatory response. To test the anti-inflammatory effects of lutein/zeaxanthin in vivo, C57BL mice were fed diets containing 0, 0.02%, and 0.1% lutein or zeaxanthin for 3 months. Macrophages were isolated from peritonea and cultured in the presence of LPS for 16 h. Levels of IL-6 and TNFα in the medium were determined. Cultured RPE produced relatively high levels of IL-6 and IL-8 even in the absence of LPS, but levels of IL-6 and TNF〈 secreted by macrophages in resting state were barely detectable. Treatment of RPE and macrophages with LPS resulted in a dramatic increase in production of IL-6, IL-8, and TNFα. Supplementation with lutein suppressed LPS-stimulated production of these inflammatory mediators in both RPE and macrophages. These suppressive effects were dose dependent. Lutein supplementation to cultured RPE also suppressed the production of IL-6 and IL-8 in the absence of LPS stimulation. Furthermore, macrophages isolated from lutein-supplemented mice produced less IL-6 and TNFα upon LPS stimulation and the suppressive effects were also dose dependent. Supplementation with zeaxanthin suppressed the production of IL-8, but not IL-6. These data indicate that lutein and zeaxanthin have anti-inflammatory effects and that increased dietary lutein or zeaxanthin intake may reduce the risk for AMD via modulating ocular and systemic inflammation.
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References
Anderson DH, Radeke MJ, Gallo NB et al (2010) The pivotal role of the complement system in aging and age-related macular degeneration: hypothesis re-visited. Prog Retin Eye Res 29:95–112
Bernstein PS (2009) Nutritional Interventions against Age-Related Macular Degeneration. Acta Hortic 841:103–112
Fernandes AF, Bian Q, Jiang JK et al (2009) Proteasome inactivation promotes p38 mitogen-activated protein kinase-dependent phosphatidylinositol 3-kinase activation and increases interleukin-8 production in retinal pigment epithelial cells. Mol Biol Cell 20:3690–3699
Fernandes AF, Guo W, Zhang X et al (2006) Proteasome-dependent regulation of signal transduction in retinal pigment epithelial cells. Exp Eye Res
Fernandes AF, Zhou J, Zhang X et al (2008) Oxidative inactivation of the proteasome in retinal pigment epithelial cells. A potential link between oxidative stress and up-regulation of interleukin-8. J Biol Chem 283:20745–20753
Hozawa A, Jacobs DR, Jr., Steffes MW et al (2007) Relationships of circulating carotenoid concentrations with several markers of inflammation, oxidative stress, and endothelial dysfunction: the Coronary Artery Risk Development in Young Adults (CARDIA)/Young Adult Longitudinal Trends in Antioxidants (YALTA) study. Clin Chem 53:447–455
Koutsos EA, Garcia Lopez JC, Klasing KC (2006) Carotenoids from in ovo or dietary sources blunt systemic indices of the inflammatory response in growing chicks (Gallus gallus domesticus). J Nutr 136:1027–1031
Li B, Ahmed F, Bernstein PS (2010) Studies on the singlet oxygen scavenging mechanism of human macular pigment. Arch Biochem Biophys 504:56–60
Patel M, Chan CC (2008) Immunopathological aspects of age-related macular degeneration. Semin Immunopathol 30:97–110
Seddon JM, Gensler G, Klein ML et al (2006) C-reactive protein and homocysteine are associated with dietary and behavioral risk factors for age-related macular degeneration. Nutrition 22:441–443
Seddon JM, Ajani UA, Sperduto RD et al (1994) Dietary carotenoids, vitamins A, C, and E, and advanced age-related macular degeneration. Eye Disease Case-Control Study Group. JAMA 272:1413–1420
Snodderly DM (1995) Evidence for protection against age-related macular degeneration by carotenoids and antioxidant vitamins. Am J Clin Nutr 62:1448 S-1461 S
Sparrow JR, Boulton M (2005) RPE lipofuscin and its role in retinal pathobiology. Exp Eye Res 80:595–606
Thomson LR, Toyoda Y, Delori FC et al (2002a) Long term dietary supplementation with zeaxanthin reduces photoreceptor death in light-damaged Japanese quail. Exp Eye Res 75:529–542
Thomson LR, Toyoda Y, Langner A et al (2002b) Elevated retinal zeaxanthin and prevention of light-induced photoreceptor cell death in quail. Invest Ophthalmol Vis Sci 43:3538–3549
van Herpen-Broekmans WM, Klopping-Ketelaars IA, Bots ML et al (2004) Serum carotenoids and vitamins in relation to markers of endothelial function and inflammation. Eur J Epidemiol 19:915–921
Wu D, Marko M, Claycombe K et al (2003) Ceramide-induced and age-associated increase in macrophage COX-2 expression is mediated through up-regulation of NF-kappa B activity. J Biol Chem 278:10983–10992
Yeum KJ, Aldini G, Chung HY et al (2003) The activities of antioxidant nutrients in human plasma depend on the localization of attacking radical species. J Nutr 133:2688–2691
Acknowledgments
We thank Kemin Industries and ZeaVison for providing lutein and zeaxanthin for dietary supplementation experiments. This work is supported by USDA AFRI Award 2009-35200-05014, NIH grant EY 011717, USDA contract 1950-510000-060-01A, and Dennis L. Gierhart Charitable Gift.
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Bian, Q., Qin, T., Ren, Z., Wu, D., Shang, F. (2012). Lutein or Zeaxanthin Supplementation Suppresses Inflammatory Responses in Retinal Pigment Epithelial Cells and Macrophages. In: LaVail, M., Ash, J., Anderson, R., Hollyfield, J., Grimm, C. (eds) Retinal Degenerative Diseases. Advances in Experimental Medicine and Biology, vol 723. Springer, Boston, MA. https://doi.org/10.1007/978-1-4614-0631-0_7
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