May 2008
Volume 49, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2008
The Effect of Ethyl Pyruvate on the Corneal Wound Healing Phenotype
Author Affiliations & Notes
  • W. J. Piluek
    Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Sciences Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • S. A. Harvey
    Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Sciences Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • R. Eberwine
    Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Sciences Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • N. Charukamnoetkanok
    Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Sciences Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • J. S. Schuman
    Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Sciences Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • N. SundarRaj
    Department of Ophthalmology, UPMC Eye Center, Eye and Ear Institute, Ophthalmology and Visual Sciences Research Center, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania
  • Footnotes
    Commercial Relationships  W.J. Piluek, None; S.A. Harvey, None; R. Eberwine, None; N. Charukamnoetkanok, None; J.S. Schuman, None; N. SundarRaj, None.
  • Footnotes
    Support  NIH grants EY03263(NS), EY08098 (core grant), Research to Prevent Blindness and The Eye and Ear Foundation of Pittsburgh, PA
Investigative Ophthalmology & Visual Science May 2008, Vol.49, 2967. doi:https://doi.org/
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      W. J. Piluek, S. A. Harvey, R. Eberwine, N. Charukamnoetkanok, J. S. Schuman, N. SundarRaj; The Effect of Ethyl Pyruvate on the Corneal Wound Healing Phenotype. Invest. Ophthalmol. Vis. Sci. 2008;49(13):2967. doi: https://doi.org/.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : Ethyl pyruvate (EP) is an aliphatic ester that is a stable derivative of pyruvic acid, an endogenous metabolite previously shown to exhibit anti-oxidative and anti-inflammatory effects. In this study, we determine the efficacy of EP in attenuating fibrosis using in vitro models of human corneal stromal wound healing.

Methods: : Primary cultures of corneal stromal keratocytes were obtained from human donor rims. Cells were arrested in G0 via starvation in serum-free media and then activated with TGF-β1 in 1% serum or β-FGF to induce the wound-healing phenotype. The expression of specific proteins was evaluated by immunocytochemical and western blotting techniques, and the relative mRNA levels were determined by quantitative real-time RT-PCR. Additionally, we performed 3 sets of microarray analysis to identify gene transcripts that are significantly altered due to treatment with EP.

Results: : At a concentration of 10-15mM, EP treatment of activated keratocytes suppressed the expression of fibrotic markers including tenascin C, fibronectin and α-smooth muscle actin. EP also inhibited activated G0-arrested corneal fibroblasts from progression beyond the G1/S phase. Microarray data revealed that EP treatment led to a downregulation of 117 genes, 68 of which are related to cell cycle regulation, DNA metabolism, cell proliferation and migration. Genes that showed robust (≥ 5 fold) upregulation included those that inhibit fibroblast proliferation, promote cell-cycle arrest, or lend protection against oxidative damage

Conclusions: : EP treatment of human corneal stromal cells attenuated the expression of certain fibrotic markers, inhibits proliferation of activated human stromal cells into myofibroblasts and suppresses other phenotypic characteristics of myofibroblasts. Microarray analysis suggests that EP functions by inhibiting genes that promote cell cycle progression and cytokinesis. Taken together, these results suggest that EP could ameliorate the fibrosis associated with the corneal wound healing response.

Keywords: cornea: stroma and keratocytes • wound healing • inflammation 
×
×

This PDF is available to Subscribers Only

Sign in or purchase a subscription to access this content. ×

You must be signed into an individual account to use this feature.

×