Lutein and zeaxanthin supplementation reduces photooxidative damage and modulates the expression of inflammation-related genes in retinal pigment epithelial cells.
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 is to test the protective effects of lutein and zeaxanthin against photooxidative damage to retinal pigment epithelial cells (RPE) and oxidation-induced changes in expression of inflammation-related genes. To mimic lipofuscin-mediated photooxidation 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- to 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 photooxidation-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 photooxidation-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 photooxidation-induced inactivation of the proteasome and photooxidation-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 photooxidation. 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.
Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA.
Qingning
Q
Bian
Shasha
S
Gao
Jilin
J
Zhou
Jian
J
Qin
Allen
A
Taylor
Elizabeth J
EJ
Johnson
Guangwen
G
Tang
Janet R
JR
Sparrow
Dennis
D
Gierhart
Fu
F
Shang
D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism; D017242:Complement Factor H / Q000235:genetics / Q000378:metabolism; D003470:Culture Media; D019587:Dietary Supplements; D015536:Down-Regulation / Q000187:drug effects / Q000528:radiation effects; D015870:Gene Expression / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D014975:Lutein / Q000378:metabolism / Q000494:pharmacology*; D008268:Macular Degeneration / Q000188:drug therapy / Q000473:pathology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000528:radiation effects*; D055668:Photochemical Processes; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D011837:Radiation-Protective Agents / Q000378:metabolism / Q000494:pharmacology*; D055213:Retinal Pigment Epithelium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D014466:Ultraviolet Rays; D024341:Xanthophylls / Q000378:metabolism / Q000494:pharmacology*; D065146:Zeaxanthins
C111835:CCL2 protein, human; C508606:CXCL8 protein, human; D018932:Chemokine CCL2; D003470:Culture Media; C508600:IL6 protein, human; D018836:Inflammation Mediators; D015850:Interleukin-6; D016209:Interleukin-8; D011837:Radiation-Protective Agents; D024341:Xanthophylls; D065146:Zeaxanthins; D017242:Complement Factor H; D046988:Proteasome Endopeptidase Complex; D014975:Lutein