April 2010
Volume 51, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2010
Up-Regulation of TGF-β1 by Vβ6 Integrin Enhances Corneal Wound Healing in Mice
Author Affiliations & Notes
  • T. Blanco
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • A. E. K. Hutcheon
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • J. D. Zieske
    Schepens Eye Research Institute, Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts
  • Footnotes
    Commercial Relationships  T. Blanco, None; A.E.K. Hutcheon, None; J.D. Zieske, None.
  • Footnotes
    Support  NIH Grant EY05665
Investigative Ophthalmology & Visual Science April 2010, Vol.51, 2497. doi:
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      T. Blanco, A. E. K. Hutcheon, J. D. Zieske; Up-Regulation of TGF-β1 by Vβ6 Integrin Enhances Corneal Wound Healing in Mice. Invest. Ophthalmol. Vis. Sci. 2010;51(13):2497.

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

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Abstract

Purpose: : Transforming Growth Factor-Beta (TGF-β) has been shown to play a key role in the wound healing process after corneal injury. After binding to αVβ6 integrin, latent TGF-β1 is activated by cleavage of the latency-associated peptide (LAP). We have previously shown that αVβ6 integrin is upregulated during epithelial wound repair in rats. The aim of this work was to evaluate the role of αVβ6 in the signaling pathway of TGF-β1 during corneal wound repair in a knockout mouse model.

Methods: : Either a 1-mm full-penetrating corneal incision or a 2-mm keratectomy were made in 129 SVE wild type mice (WT) and β6-null mice and allowed to heal for up to 4 weeks. The pattern of corneal barrier restoration was studied "in vivo" by slit lamp and in tissue sections by means of both optical and electron microscopy. In addition, α-SMA, TGF-β1, αVβ6 and laminin were evaluated by both indirect-immunofluorescence microscopy and western blot analysis.

Results: : After keratectomy, a significant delay of epithelial resurfacing and basement membrane restoration was observed in the β6-null mice compared to WT. After incision, the wound area of the β6-null mouse corneas was repopulated only by epithelium and minimal amounts of newly synthesized matrix, whereas in WT, the corneal integrity was fully restored. A significant down-regulation of α-SMA, mature TGF-β1 and laminin, and no αVβ6 was observed in the β6-null mice compared to WT. However, higher amounts of large latent TGF-β1 were observed in the β6-null mice than WT.

Conclusions: : αVβ6 might play a key role in the corneal wound-healing process by binding latent TGF-β1 and assembling subepithelial basement membrane.

Keywords: wound healing • cornea: epithelium • cornea: stroma and keratocytes 
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