May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
Curcumin and Celecoxib Protect the Retina From Light and Oxidant Stress-Mediated Cell Death
Author Affiliations & Notes
  • R. E. Anderson
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
    Ophthalmology/Cell Biology,
  • C. V. Rao
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
    OU Cancer Institute,
  • J. R. Patlolla
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
    OU Cancer Institute,
  • L. Zheng
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
    Ophthalmology,
  • J.-T. A. Tran
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
    Ophthalmology,
  • M. P. Agbaga
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
    Cell Biology,
  • M. N. A. Mandal
    Univ of Oklahoma Hlth Sci Ctr, Oklahoma City, Oklahoma
    Ophthalmology,
  • Footnotes
    Commercial Relationships  R.E. Anderson, None; C.V. Rao, None; J.R. Patlolla, None; L. Zheng, None; J.A. Tran, None; M.P. Agbaga, None; M.N.A. Mandal, None.
  • Footnotes
    Support  EY04149, EY00871, EY12190, RR17703, Research to Prevent Blindness, Inc.; Foundation Fighting Blindness, CA94962, Knights Templar Eye Foundation; OU College of Medicine Alumni Association
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 4391. doi:https://doi.org/
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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. doi: https://doi.org/.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : 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.

Methods: : 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.

Results: : 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.

Conclusions: : 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.

Keywords: neuroprotection • retinal degenerations: cell biology • oxidation/oxidative or free radical damage 
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