Cyp1b1 mediates periostin regulation of trabecular meshwork development by suppression of oxidative stress

Yun Zhao, Shoujian Wang, Christine M. Sorenson, Leandro Teixeira, Richard R. Dubielzig, Donna M. Peters, Simon J. Conway, Colin R. Jefcoate, Nader Sheibani

Research output: Contribution to journalArticle

35 Scopus citations

Abstract

Mutation in CYP1B1 has been reported for patients with congenital glaucoma. However, the underlying mechanisms remain unknown. Here we show increased diurnal intraocular pressure (IOP) in Cyp1b1-deficient (Cyp1b1-/-) mice. Cyp1b1-/- mice presented ultrastructural irregular collagen distribution in their trabecular meshwork (TM) tissue along with increased oxidative stress and decreased levels of periostin (Postn). Increased levels of oxidative stress and decreased levels of Postn were also detected in human glaucomatous TM tissues. Furthermore, Postn-deficient mice exhibited TM tissue ultrastructural abnormalities similar to those of Cyp1b1-/- mice. Administration of the antioxidant N-acetylcysteine (NAC) restored structural abnormality of TM tissue in Cyp1b1-/- mice. In addition, TM cells prepared from Cyp1b1-/- mice exhibited increased oxidative stress, altered adhesion, and decreased levels of Postn. These aberrant cellular responses were reversed in the presence of NAC or by restoration of Cyp1b1 expression. Cyp1b1 knockdown or inhibition of CYP1B1 activity in Cyp1b1-/- TM cells resulted in a Cyp1b1-/- phenotype. Thus, metabolic activity of CYP1B1 contributes to oxidative homeostasis and ultrastructural organization and function of TM tissue through modulation of Postn expression.

Original languageEnglish (US)
Pages (from-to)4225-4240
Number of pages16
JournalMolecular and cellular biology
Volume33
Issue number21
DOIs
StatePublished - 2013

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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