June 2013
Volume 54, Issue 15
Free
ARVO Annual Meeting Abstract  |   June 2013
TNFα is required for normal tissue repair in injured mouse conjunctiva
Author Affiliations & Notes
  • Osamu Yamanaka
    Ophthalmology, Wakayama Medical University, Wakayama, Japan
  • Ai Kitano
    Ophthalmology, Wakayama Medical University, Wakayama, Japan
  • Yuka Okada
    Ophthalmology, Wakayama Medical University, Wakayama, Japan
  • Winston Kao
    Ophthalmology, University of Cincinnati, Cincinnati, OH
  • Shizuya Saika
    Ophthalmology, Wakayama Medical University, Wakayama, Japan
  • Footnotes
    Commercial Relationships Osamu Yamanaka, None; Ai Kitano, None; Yuka Okada, None; Winston Kao, None; Shizuya Saika, None
  • Footnotes
    Support None
Investigative Ophthalmology & Visual Science June 2013, Vol.54, 2111. doi:
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    • Get Citation

      Osamu Yamanaka, Ai Kitano, Yuka Okada, Winston Kao, Shizuya Saika; TNFα is required for normal tissue repair in injured mouse conjunctiva. Invest. Ophthalmol. Vis. Sci. 2013;54(15):2111.

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

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Abstract

Purpose: To examined the roles of TNFα, a major proinflammatory cytokine, in the process of tissue repair in mouse conjunctiva in vivo and the fibrogenic responses of of cultured human subconjunctival fibroblasts (hSCFs) as well.

Methods: A circumferential incision was made in the equatorial conjunctiva of the right eye of generally anesthetized TNFα-null (KO) and wild-type (WT) mice using scissors. At 2, 5, 7 and 10 days, the eyes were processed for histology and immunohistochemistry to evaluate the tissue repair process. Expression of type I collagen and growth factors was evaluated by real time PCR (RT-PCR). The effects of TNFα (10 ng/ml) on production of a smooth muscle actin (αSMA) and type I collagen and Smad3 phosphorylation using cultured hSCFs with or without TGFβ1 (5 ng/ml) were also studied. Effects of TNFα on hSCFs proliferation, migration and Erk activation were finally examined.

Results: TNFα KO mice showed severe macrophage invasion, marked generation of myofibroblasts in healing subconjuncitval tissue and upregulation of mRNAs of fibrogenic components, i. e., TGFβ1, CTGF and Col1a2 chain in comparison to those of WT mice. In vitro experiments with cultured hSCFs showed that TNFα suppressed the protein expression of αSMA and type I collagen, as well as Smad3 phosphorylation, upon TGFβ1 stimulation. TNFα activated Erk signal and enhance cell migration and proliferation.

Conclusions: Expression of TNFα in situ has an essential role for normal tissue repair in mouse conjunctiva and ablation of TNFα in mice leads to excess inflammation and tissue fibrosis. Administration of counteracts TGFβ1/Smad3 activation, and stimulates Erk activation and proliferation and migration of TNFα to cultured hSCFs that may account for manifestations in the wound healing excess inflammation and fibrosis seen in TNFα null mice.

Keywords: 765 wound healing • 519 extracellular matrix • 714 signal transduction  
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