May 2006
Volume 47, Issue 13
Free
ARVO Annual Meeting Abstract  |   May 2006
The Mechanism of Corneal Epithelium Wound Healing Delay in TGF–Beta Type II Receptor Conditional Knock–Out Mice
Author Affiliations & Notes
  • T. Kazuto
    Ophthalmology, Kyoto, Kyoto, Japan
  • Y. Hayashi
    Ophthalmology, University of Cincinnati, Cincinnati, OH
  • T.–I. Chikama
    Ophthalmology, University of Cincinnati, Cincinnati, OH
  • N. Terai
    Ophthalmology, Kyoto, Kyoto, Japan
  • W.W. Y. Kao
    Ophthalmology, University of Cincinnati, Cincinnati, OH
  • Footnotes
    Commercial Relationships  T. Kazuto, None; Y. Hayashi, None; T. Chikama, None; N. Terai, None; W.W.Y. Kao, None.
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science May 2006, Vol.47, 5028. doi:
  • Views
  • Share
  • Tools
    • Alerts
      ×
      This feature is available to authenticated users only.
      Sign In or Create an Account ×
    • Get Citation

      T. Kazuto, Y. Hayashi, T.–I. Chikama, N. Terai, W.W. Y. Kao; The Mechanism of Corneal Epithelium Wound Healing Delay in TGF–Beta Type II Receptor Conditional Knock–Out Mice . Invest. Ophthalmol. Vis. Sci. 2006;47(13):5028.

      Download citation file:


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

      ×
  • Supplements
Abstract

Purpose: : We previously reported that healing of epithelium debridement was delayed in mouse cornea epithelium lacking TGF–ß type II receptor (Tbr2) by conditional knock–out, due to inhibition of cell migration suppression albeit an up–regulation of cell proliferation The purpose of this study is to determine molecular mechanisms accountable for the observations.

Methods: : TGF–ß type II receptor (Tbr2) floxed mice were bred with Krt12–Cre mice to generate bitransgenic mice in which the TGF–ß receptor 2 gene (Tbr2) was disrupted selectively in the corneal epithelial cells. Corneal epithelial debridement (2 mm diameter) was created in 2–month–old bitransgenic Tbr2ceΔ/ceΔ (Krt12Cre/CreTbR2f/f) mice and their littermates as controls Tbr2ceΔ/w (Krt12Cre/CreTbR2f/w) and Tbr2w/w (Krt12Cre/CreTbR2w/w). Immunohistochemistry with anti–p–cJun and ActivinR1B antibody was performed to elucidate their roles in wound healing. Smad4 floxed mice were also bred with Krt12–Cre mice to generate bitransgenic mice in which the Smad4 gene was disrupted selectively in the corneal epithelial cells. Corneal epithelial debridement was created in 2–month–old bitransgenic Smad4ceΔ/ceΔ (Krt12Cre/CreSmad4f/f) mice and their littermates as controls Smad4ceΔ/w (Krt12Cre/CreSmad4f/w) and Smad4w/w (Krt12Cre/CreSmad4w/w).

Results: : The result of phospo–cJun immunohistochemistry shows that cJun activation in early phase of corneal epithelium wound healing is suppressed in Tbr2ceΔ/ceΔ mice than those of littermate controls. The result of activin R1B immunohistochemistry shows a prolong up–regulation of activin R1B expression up to 48 h after wounding in Tbr2ceΔ/ceΔ whereas in controls the up–regulation of activin R1B returned to basal level by 48 hrs of wounding. Smad4ceΔ/ceΔ mice did not show any wound healing delay comparing with controls.

Conclusions: : Our results indicate that Smad cascade does not play a significant role in corneal epithelium wound healing. Our data are consistent with the notion that p38 activation mediates the TGFß signaling, which may account for cell migration and inhibition of cell proliferation during healing of epithelium debridement.

Keywords: cornea: epithelium • transgenics/knock-outs • wound healing 
×
×

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.

×