Proteasome inhibition by chronic oxidative stress in human trabecular meshwork cells.

Journal Article (Journal Article)

The pathophysiologic mechanisms leading to the malfunction of the trabecular meshwork (TM)-Schlemm's canal (SC) outflow pathway in glaucoma are still unclear. We hypothesize that chronic oxidative stress may contribute to the malfunction of the outflow pathway by impairing the intracellular proteasome system of the cells, decreasing the ability of the tissue to modulate outflow resistance. To study the effects of chronic oxidative stress on proteasome function, primary cultures of human TM cells were incubated under 40% oxygen and proteasome activity was analyzed by measuring the accumulation of enhanced green fluorescent protein fused to a PEST motif. Changes in proteasome content, cellular senescence, and cell viability were also monitored. After 10 days of exposure to chronic oxidative stress, TM cells showed a marked decline in proteasome activity that was associated with premature senescence and decreased cell viability. These results suggest that proteasome failure may be involved in glaucoma pathophysiology.

Full Text

Duke Authors

Cited Authors

  • Caballero, M; Liton, PB; Epstein, DL; Gonzalez, P

Published Date

  • August 22, 2003

Published In

Volume / Issue

  • 308 / 2

Start / End Page

  • 346 - 352

PubMed ID

  • 12901875

International Standard Serial Number (ISSN)

  • 0006-291X

Digital Object Identifier (DOI)

  • 10.1016/s0006-291x(03)01385-8


  • eng

Conference Location

  • United States