May 2007
Volume 48, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2007
Effect of Overexpression of PPAR Gamma on Smad Signal in Fibroblasts and Macrophages and on the Healing Process of Corneal Alkali Burn in Mice
S. Saika; K. Ikeda; O. Yamanaka; Y. Okada; T. Miyamoto; A. Kitano; Y. Ohnishi; W. W.-. Y. Kao
Author Affiliations & Notes
  • S. Saika
    Ophthalmology, Wakayama Med. Univ., Wakayama, Japan
  • K. Ikeda
    Anatomy, Osaka City Univ., Osaka, Japan
  • O. Yamanaka
    Ophthalmology, Wakayama Med. Univ., Wakayama, Japan
  • Y. Okada
    Ophthalmology, Wakayama Med. Univ., Wakayama, Japan
  • T. Miyamoto
    Ophthalmology, Wakayama Med. Univ., Wakayama, Japan
  • A. Kitano
    Ophthalmology, Wakayama Med. Univ., Wakayama, Japan
  • Y. Ohnishi
    Ophthalmology, Wakayama Med. Univ., Wakayama, Japan
  • W. W.-. Y. Kao
    Ophthalmology, Univ. of Cincinnati Med. Ctr., Cincinnati, Ohio
  • Footnotes
    Commercial Relationships S. Saika, None; K. Ikeda, None; O. Yamanaka, None; Y. Okada, None; T. Miyamoto, None; A. Kitano, None; Y. Ohnishi, None; W.W.Y. Kao, None.
  • Footnotes
    Support None.
Investigative Ophthalmology & Visual Science May 2007, Vol.48, 1476. doi:
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      S. Saika, K. Ikeda, O. Yamanaka, Y. Okada, T. Miyamoto, A. Kitano, Y. Ohnishi, W. W.-. Y. Kao; Effect of Overexpression of PPAR Gamma on Smad Signal in Fibroblasts and Macrophages and on the Healing Process of Corneal Alkali Burn in Mice. Invest. Ophthalmol. Vis. Sci. 2007;48(13):1476.

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Abstract

Purpose:: To examine the effects of adenoviral overexpression of peroxisome proliferator-activated receptor gamma (PPARg) on cell behaviors of ocular fibroblasts, macrophages and corneal epithelial cells in vitro and also to examine if topical PPARg-adenovirus (Ad) has anti-inflammatory and anti-fibrogenic effects in an alkali-burned mouse cornea.

Methods:: Cultured mouse ocular fibroblasts, macrophages and SV40-immortalized corneal epithelial cell line received PPARg-Ad and were treated with TGFb1 after 48 hrs. Smad signal and fibrogenesis-related gene expression were assayed by using immunocytochemistry, western blotting or real-time RT-PCR. A mouse cornea (n = 75) burned with 1N NaOH was allowed to heal for day 5, 10 and 20 after receiving topical PPARg-Ad or control Ad. Inflammation and fibrogenic reaction in tissue were examined by using histology and immunohistochemistry. Fibrogenesis-related gene expression were assayed by using real-time RT-PCR.

Results:: PPARg overexpression suppressed expression of inflammation-related or scarring-related growth factors and matrix metalloproteinases (MMPs) in macrophages, fibroblasts and corneal epithelial cells. It also reduced expression of collagen Ia2 mRNA and fibronectin in fibroblasts. PPARg-Ad inhibited its nuclear translocation of phospho-Smad2 in the cell types in vitro. Topical PPARg-Ad suppressed up-regulation of growth factors and MMP-2, and reduced invasion of macrophages and suppressed myofibroblast generation in a healing burned cornea. Re-epihtleialization in the healing cornea was also promoted by PPARg-Ad.

Conclusions:: Adenoviral gene transfer of PPARg has a therapeutic effect on experimental corneal alkali burn. The mechanism of action might include suppression of activation of fibroblasts and macrophages with reduction of TGFb/Smad signal.

Keywords: cornea: basic science • wound healing • gene transfer/gene therapy 
© 2007, The Association for Research in Vision and Ophthalmology, Inc., all rights reserved. Permission to republish any abstract or part of an abstract in any form must be obtained in writing from the ARVO Office prior to publication.
Copyright © 2024 Association for Research in Vision and Ophthalmology.
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