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S. Gao, Q. Bian, J. Zhou, J. Qin, A. Taylor, E. J. Johnson, G. Tang, J. R. Sparrow, D. L. Gierhart, F. Shang; Zeaxanthin Supplementation Reduces Photo-Oxidative Damage and Modulates the Expression of Inflammation-Related Genes in Retinal Pigment Epithelial Cells. Invest. Ophthalmol. Vis. Sci. 2010;51(13):1431.
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Oxidative damage and excessive inflammatory responses are etiologically related to the pathogenesis of AMD. Epidemiologic studies suggest that insufficient dietary zeaxanthin intake increase the risk for AMD. The objective of this work is to test the protective effects of zeaxanthin against photo-oxidative damage to RPE and oxidation-induced changes in expression of inflammation-related genes.
To mimic lipofuscin-mediated photo-oxidation in vivo, cultured ARPE-19 cells were allowed to accumulate A2E, the major fluorophore and photosensitizer of lipofuscin, for 10 days and then cultured in the presence or absence of 10 µM zeaxanthin for an additional 3 days. The cells were then exposed to blue light for 10 min, followed by 6 h recovery in normal medium. The levels of mRNA and proteins of IL-6, IL-8, MCP-1 and complement factor H (CFH) were determined by real-time RT-PCR and ELISA, respectively. Proteasome activity in the cells was measured using fluorogenic peptides as substrates.
Exposure of RPE to blue light alone had no detectable effect on expression of IL-6, IL-8, MCP-1 and CFH. Exposure of RPE to A2E alone increased the expression of IL-8 and MCP-1 by 2-fold. In contrast, exposure of A2E-containing RPE to blue light resulted in 50-80% decrease in expression of CFH and MCP-1 and ~ 20-fold increase in expression of IL-8. Exposure of A2E-containing RPE to blue light also resulted in 40-60% decrease in proteasome activity. However, pre-incubation of the A2E-containing RPE with zeaxanthin significantly attenuated the photo-oxidation-induced inactivation of the proteasome and photo-oxidation induced changes in expression of IL-6, IL-8, MCP-1 and CFH. The photo-oxidation-induced changes in expression of MCP-1, IL-8 and CFH are similar to those caused by chemical inhibition of the proteasome, indicating that zeaxanthin modulates photo-oxidation-induced alterations in expression of MCP-1, IL-8 and CFH partially via protecting the proteasome from inactivation. Furthermore, supplementation of zeaxanthin to cultured RPE cells also reduced the expression of IL-6 and IL-8 induced by LPS.
These data indicate that zeaxanthin modulates inflammatory responses in cultured RPE in proteasome-dependent and proteasome-independent manners. The anti-inflammatory effects of zeaxanthin may be a mechanism by which it protects against AMD.
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