PRDX6 attenuates oxidative stress-and TGF-induced abnormalities of human trabecular meshwork cells

Nigar Fatma, Eri Kubo, Carol B Toris, W. D. Stamer, Carl B. Camras, Dhirendra P Singh

Research output: Contribution to journalArticle

36 Scopus citations

Abstract

Oxidative stress and TGF-induced disturbance of cells and tissues are implicated in initiation and progression of pathophysiology of cells/tissues. Using primary human Trabecular Meshwork (TM) cells from normal and glaucomatous subjects, this study demonstrated that peroxiredoxin (PRDX) 6, an antioxidant, offsets the deleterious effects of oxidative stress on TM cells by optimizing ROS and TGF levels. An analysis of glaucomatous TM cells revealed a reduced expression of PRDX6 mRNA and protein. Biochemical assays disclosed enhanced levels of ROS, as well as high levels of TGFs and these cells expressed elevated extracellular matrix (ECM) and Tsp1 proteins with reduced MMP2; conditions implicated in the pathophysiology of glaucoma. Non-glaucomatous TM cells exposed to TGFs/ROS showed similar features as in glaucomatous cells. The abnormalities induced were reversed by delivery of PRDX6. The data provide evidence that oxidative stress-induced abnormality in TM may be related to reduced PRDX6 expression and provide a foundation for antioxidant-based therapeutics for treating glaucoma.

Original languageEnglish (US)
Pages (from-to)783-795
Number of pages13
JournalFree Radical Research
Volume43
Issue number9
DOIs
StatePublished - Nov 30 2009

    Fingerprint

Keywords

  • Antioxidant
  • Extracellular matrix proteins
  • Peroxiredoxin 6
  • Reactive oxygen species
  • Transforming growth factor

ASJC Scopus subject areas

  • Biochemistry

Cite this