April 2011
Volume 52, Issue 14
Free
ARVO Annual Meeting Abstract  |   April 2011
Quantitative Proteomic Studies Implicate Mitochondrial Dysfunction in the Trabecular Meshwork in Glaucoma Pathology
Author Affiliations & Notes
  • John W. Crabb
    Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
    Ophthalmology and Molecular Medicine, Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, Cleveland, Ohio
  • Xianglin Yuan
    Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
  • John S. Crabb
    Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
  • Tasneem M. Putliwala
    Cell Biology and Anatomy, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas
  • Abbot F. Clark
    Cell Biology and Anatomy, North Texas Eye Research Institute, University of North Texas Health Science Center, Fort Worth, Texas
  • Kathryn E. Bollinger
    Cole Eye Institute, Cleveland Clinic, Cleveland, Ohio
    Ophthalmology, Medical College of Georgia, Augusta, Georgia
  • Footnotes
    Commercial Relationships  John W. Crabb, Allergan, Inc. (C); Xianglin Yuan, None; John S. Crabb, None; Tasneem M. Putliwala, None; Abbot F. Clark, None; Kathryn E. Bollinger, None
  • Footnotes
    Support  Supported in part by NIH grants EY018147, EY14239, EY15638, Challenge grant Research to Prevent Blindness (RPB), American Health Assistance Fndn grant 34-0714585 and RPB Sr Investigator Award to JWC.
Investigative Ophthalmology & Visual Science April 2011, Vol.52, 6611. doi:
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      John W. Crabb, Xianglin Yuan, John S. Crabb, Tasneem M. Putliwala, Abbot F. Clark, Kathryn E. Bollinger; Quantitative Proteomic Studies Implicate Mitochondrial Dysfunction in the Trabecular Meshwork in Glaucoma Pathology. Invest. Ophthalmol. Vis. Sci. 2011;52(14):6611.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose: : Toward understanding of the molecular basis of primary open angle glaucoma (POAG) and steroid-induced secondary OAG, we quantified proteomic changes in trabecular meshwork (TM) cells following treatment with transforming growth factor β2 (TGF-β2) or dexamethasone (Dex).

Methods: : Primary cultures of TM cells from four human donors were treated with TGF-β2 or with Dex and analyzed by LC MS/MS iTRAQ technology. Protein quantitation required ≥ 2 unique peptides per protein and utilized code written in R. Proteins present in ≥ 3 cell samples and exhibiting average protein ratios above or below the mean by at least 1 SD and p values < 0.06 were considered of higher or lower abundance.

Results: : Several mitochondrial proteins were significantly changed in TM cells by either TGF-β2 or Dex, including one elevated and 7 reduced by TGF-β2 and 6 elevated and 2 reduced by Dex. Six mitochondrial proteins were potentially altered by both treatments, including superoxide dismutase 2 and sulfide:quinone oxidoreductase. Four other proteins were significantly altered by both treatments, including paladin and prolyl 4-hydroxylase α1 and α2.

Conclusions: : Mitochondrial proteomic changes induced by TGF-β2 or Dex implicate mitochondrial dysfunction in TM cells as a contributing factor to TM senescence and/or oxidative damage in the aqueous humor outflow pathway leading to elevated intraocular pressure in POAG. Other proteomic changes support ECM remodeling and disrupted cytoskeletal and cell-cell interactions in glaucoma pathology. Common physiological consequences of TGF-β2- and Dex-treatments may account in part for increased risk of OAG in steroid responders.

Keywords: proteomics • trabecular meshwork • mitochondria 
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