|Bian, Qingning -|
|Gao, Shasha -|
|Zhou, Jilin -|
|Qin, Jian -|
|Taylor, Allen -|
|Johnson, Elizabeth -|
|Tang, Guangwen -|
|Sparrow, Janet -|
|Gierhart, Dennis -|
|Shang, Fu -|
Submitted to: Free Radicals in Biology and Medicine
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: May 4, 2011
Publication Date: August 15, 2011
Citation: Bian, Q., Gao, S., Zhou, J., Qin, J., Taylor, A., Johnson, E.J., Tang, G., Sparrow, J.R., Gierhart, D., Shang, F. 2011. Lutein and zeaxanthin supplementation reduces photo-oxidative damage and modulates the expression of inflammation related genes in retinal pigment epithelial cells. Free Radicals in Biology and Medicine. 53(6):1298-1307. Interpretive Summary: There are many advantages to consuming higher levels of lutein. Among these is possibly the decreased risk for age related macular degeneration (AMD). In this study, we used cell culture systems to better understand why intake of higher levels of lutein is associated with enhanced eye health. We found that lutein or zeaxanthin modulates inflammatory responses in cultured RPE cells in response to photooxidative stress. Protecting the protein degrading machinery from oxidative inactivation appears to be one of the mechanisms by which lutein and zeaxanthin modulate the inflammatory response. Because AMD is related to inflammatory stress, similar mechanisms may explain beneficial effects of lutein and zeaxanthin in reducing the risk for AMD.
Technical Abstract: Oxidative damage and inflammation are related to the pathogenesis of age-related macular degeneration (AMD). Epidemiologic studies suggest that insufficient dietary lutein and zeaxanthin intake or lower serum zeaxanthin levels are associated with increased risk for AMD. The objective of this work was to test the protective effects of lutein and zeaxanthin against photo-oxidative damage to retinal pigment epithelial cells (RPE) and oxidation-induced changes in expression of inflammation-related genes. To mimic lipofuscin-mediated photo-oxidation in vivo, we used ARPE-19 cells that accumulated A2E, a lipofuscin fluorophore and photosensitizer, as a model system to investigate the effects of lutein and zeaxanthin supplementation. The data show that supplementation with lutein or zeaxanthin in the medium resulted in accumulation of lutein or zeaxanthin in the RPE cells. The concentrations of lutein and zeaxanthin in the cells were 2-14-fold of that detected in the medium, indicating that ARPE-19 cells actively take up lutein or zeaxanthin. As compared with untreated cells, exposure of A2E-containing RPE to blue light resulted in a 40-60% decrease in proteasome activity, a 50-80% decrease in expression of CFH and MCP-1, and an ~ 20-fold increase in expression of IL-8. The photo-oxidation-induced changes in expression of MCP-1, IL-8 and CFH were similar to those caused by chemical inhibition of the proteasome, suggesting that inactivation of the proteasome is involved in the photo-oxidation-induced alteration in expression of these inflammation-related genes. Incubation of the A2E-containing RPE with lutein or zeaxanthin prior to blue light exposure significantly attenuated the photo-oxidation-induced inactivation of the proteasome and photo-oxidation induced changes in expression of MCP-1, IL-8, and CFH. Together, these data indicate that lutein or zeaxanthin modulates inflammatory responses in cultured RPE in response to photo-oxidation. Protecting the proteasome from oxidative inactivation appears to be one of the mechanisms by which lutein and zeaxanthin modulate the inflammatory response. Similar mechanisms may explain salutary effects of lutein and zeaxanthin in reducing the risk for AMD.