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R. E. Anderson, C. V. Rao, J. R. Patlolla, L. Zheng, J.-T. A. Tran, M. P. Agbaga, M. N. A. Mandal; Curcumin and Celecoxib Protect the Retina From Light and Oxidant Stress-Mediated Cell Death. Invest. Ophthalmol. Vis. Sci. 2008;49(13):4391.
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Oxidant stress and inflammation is being established as important components in the pathogenesis of age-related macular degeneration (AMD). The purpose of this study was to test the protective role of curcumin and celecoxib, two chemopreventive anti-inflammatory compounds, in a light-induced retinal degeneration model.We also tested the protective roles of these compounds in cultures of mouse retina- and human RPE-derived cell lines 661W and ARPE-19 cells, respectively, from oxidant stress-induced cell death.
Wistar rats, 5-6-week-old age, born and reared in cyclic dim light (5-10 lux), were fed with lab diets (AIN-76A) with 2000 ppm curcumin or 1000 ppm celecoxib for two weeks. The rats were then exposed to 1,000 lux light for 3 hours. After light stress, retinal function was measured by electroretinography (ERG), and eyes and retinas were harvested for histology, gene expression analysis, and protein studies. The 661W cells and ARPE-19 cells were treated with curcumin (20 µM) or celecoxib (40 µM), followed by varying concentration of H2O2 (0.25 - 2 mM) for 6 h. Cell death was determined by lactate dehydrogenase (LDH) release assay. Expression of genes involved in inflammation, oxidative-stress, and cell-death was determined in retinal and 661W samples by qRT-PCR. Inflammatory pathway proteins were determined by Western blotting.
The light-damage paradigm we used caused degeneration of ~50% of photoreceptor cells with maximum effect on the superior central region. Both curcumin and celecoxib exerted significant protection of retinal function (80-90%, p<0.01, by ERG) and morphology. We observed suppression of inflammatory genes such as Icam1, Timp1, Ccl2, Lox12, and Cox2, and of the apoptotic gene Fosl1, and up-regulation of protective genes like thioredoxin in the retina of rats fed the supplemented diets. Both compounds showed significant protection of 661W and ARPE-19 cells (p<0.01) from H2O2-mediated cytotoxicity.
Curcumin, an inhibitor of Cox2 and NfkB mediated inflammation, and celecoxib, a specific inhibitor of Cox2, can protect the rat retina from light-induced cell death, and retina- and RPE-derived cells from oxidant stress-induced cell death by blocking activation of inflammatory pathway genes. These compounds could be potential candidates for augmentative therapy of AMD.
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