Proteomic similarities in steroid responsiveness in normal and glaucomatous trabecular meshwork cells

Kathryn E. Bollinger, John S. Crabb, Xianglin Yuan, Tasneem Putliwala, Abbot F. Clark, John W. Crabb

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

Purpose: Glucocorticoids (GCs) are common anti-inflammatory agents that can cause ocular hypertension and secondary glaucoma as a consequence of impaired aqueous humor outflow through the trabecular meshwork (TM). Mechanisms of GC-signaling are complex and poorly understood. To better understand GC-signaling in the eye, we tested the hypothesis that common mechanisms of steroid responsiveness exist in TM cells from normal and glaucomatous donors. Methods: Four primary cultures of human TM cells from normal and glaucomatous donors were treated with or without dexamethasone (Dex) for 10 days, then cellular proteins were extracted, identified and quantified by liquid chromatography tandem mass spectrometry (LC MS/MS) iTRAQ (isobaric tags for relative and absolute quantitation) technology. Results: A total of 718 proteins were quantified. Dex-treatment significantly altered the abundance of 40 proteins in ≥3 cell samples, 37 of which have not previously been associated with GC-signaling in TM cells. Most steroid responsive proteins were changed in all four TM cells analyzed, both normal and glaucomatous. GC-induced proteomic changes support remodeling of the extracellular matrix, disorganization of the cytoskeleton/cell-cell interactions, and mitochondrial dysfunction. Such physiologic consequences appear common to those induced in TM cells by transforming growth factor-β2, another putative contributor to ocular hypertension and glaucoma pathology. Conclusions: The results expand the repertoire of TM proteins involved in GC-signaling, demonstrate common consequences of GC-signaling in normal and glaucomatous TM cells, and reveal similarities in proteomic changes induced by steroids and TGFβ2 in normal and glaucomatous TM cells. Finally, the data contributes to a TM quantitative proteomic database.

Original languageEnglish (US)
Pages (from-to)2001-2011
Number of pages11
JournalMolecular Vision
Volume18
StatePublished - Jul 20 2012
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology

Fingerprint Dive into the research topics of 'Proteomic similarities in steroid responsiveness in normal and glaucomatous trabecular meshwork cells'. Together they form a unique fingerprint.

  • Cite this

    Bollinger, K. E., Crabb, J. S., Yuan, X., Putliwala, T., Clark, A. F., & Crabb, J. W. (2012). Proteomic similarities in steroid responsiveness in normal and glaucomatous trabecular meshwork cells. Molecular Vision, 18, 2001-2011.