Sustained stress response after oxidative stress in trabecular meshwork cells.

Published online

Journal Article

PURPOSE: To investigate the mechanisms by which chronic oxidative stress may lead to a sustained stress response similar to that previously observed in the trabecular meshwork (TM) of glaucoma donors. METHODS: Porcine TM cells were treated with 200 microM H2O2 twice a day for four days and were allowed to recover for three additional days. After the treatment, TM cells were analyzed for generation of intracellular reactive oxygen species (iROS), mitochondrial potential, activation of NF-kappaB, and the expression of inflammatory markers IL-1alpha, IL-6, IL-8, and ELAM-1. Potential sources of iROS were evaluated using inhibitors for nitric oxide, nitric oxide synthetase, cyclooxygenase, xanthine oxidase, NADPH oxidase, mitochondrial ROS, and PKC. The role of NF-kappaB activation in the induction of inflammatory markers was evaluated using the inhibitors Lactacystin and BAY11-7082. RESULTS: Chronic oxidative stress simulated by H2O2 exposure of porcine TM cells resulted in the sustained production of iROS by the mitochondria. Inhibition of mitochondrial iROS had a significant inhibitory effect on the activation of NF-kappaB and the induction of IL-1alpha, IL-6, IL-8, and ELAM-1 triggered by chronic oxidative stress. Inhibition of NF-kappaB partially prevented the induction of IL-1alpha, IL-8, and ELAM-1, but not IL-6. CONCLUSIONS: Chronic oxidative stress in TM cells induced iROS production in mitochondria. This increase in iROS may contribute to the pathogenesis of the TM in glaucoma by inducing the expression of inflammatory mediators previously observed in glaucoma donors as well as the levels of oxidative damage in the tissue.

Full Text

Duke Authors

Cited Authors

  • Li, G; Luna, C; Liton, PB; Navarro, I; Epstein, DL; Gonzalez, P

Published Date

  • December 17, 2007

Published In

Volume / Issue

  • 13 /

Start / End Page

  • 2282 - 2288

PubMed ID

  • 18199969

Pubmed Central ID

  • 18199969

Electronic International Standard Serial Number (EISSN)

  • 1090-0535

Language

  • eng

Conference Location

  • United States