April 2009
Volume 50, Issue 13
Free
ARVO Annual Meeting Abstract  |   April 2009
Down-Regulation of Pten Accelerates Corneal Wound Healing Through Increased Cell Migration
Author Affiliations & Notes
  • M. Zhao
    Dermatology and Ophthalmology,
    University of California, Davis, Davis, California
  • L. Cao
    Dermatology,
    University of California, Davis, Davis, California
  • E. Hernandez
    Ophthalmology,
    University of California, Davis, Davis, California
  • V. Tran
    Dermatology,
    University of California, Davis, Davis, California
  • B. Reid
    Dermatology,
    University of California, Davis, Davis, California
  • J. Pu
    School of Medical Sciences and Department of Ophthalmology, University of Aberdeen, Aberdeen, United Kingdom
  • M. Mannis
    Ophthalmology,
    University of California, Davis, Davis, California
  • Footnotes
    Commercial Relationships  M. Zhao, None; L. Cao, None; E. Hernandez, None; V. Tran, None; B. Reid, None; J. Pu, None; M. Mannis, None.
  • Footnotes
    Support  Dermatology start up fund
Investigative Ophthalmology & Visual Science April 2009, Vol.50, 3493. doi:
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      M. Zhao, L. Cao, E. Hernandez, V. Tran, B. Reid, J. Pu, M. Mannis; Down-Regulation of Pten Accelerates Corneal Wound Healing Through Increased Cell Migration. Invest. Ophthalmol. Vis. Sci. 2009;50(13):3493.

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

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Abstract

Purpose: : The tumor suppressor phosphatase and tensin homolog (PTEN) negatively regulates the phosphatidylinositol 3-kinase (PI3K)/Akt pathway. PI3K/PTEN play critical roles in cell polarization and directional cell migration, suggesting PTEN’s significant role in wound healing where spatially organized tissue growth is essential. We tested the hypothesis that wounding down-regulates PTEN and that the down-regulation enhances wound healing.

Methods: : Western blotting and immunofluorescence staining were used to determine the expression of PTEN at wounds in human corneal epithelial (HCE) monolayer and rat corneas. Time-lapse imaging was used to monitor cell migration, wound closure and the effects of inhibitors for PTEN and/or pAkt.

Results: : Wounding significantly reduced PTEN expression, which persisted for several hours in HCE monolayer cultures as revealed with Western. Down-regulation of PTEN was also observed in both monolayer wounds and in-vivo corneal wounds when detected with immunoflurescence staining. Inhibition of PTEN with bpv (di-potassium bisperoxo (picolinato) oxovanadate) resulted in significant activation of the PI3K/Akt signaling pathway. Migration rates of individual cells increased from 8.8µm to 17.3µm/hr (p<0.05). Application of bpv (1.0µM and 10.0µM) significantly increased the healing rate of corneal epithelial wound in both human monolayer and in rat eye organ cultures (p<0.05).

Conclusions: : Injury to the cornea down-regulated PTEN expression and activated PI3K/Akt signaling. This down-regulation contributed significantly to enhanced cell migration in wound healing. Inhibition of PTEN resulted in acceleration of HCE cell migration and corneal wound closure mediated by the PI3 kinase/Akt pathway. Inhibition of PTEN may therefore be an effective treatment for corneal wound healing.

Keywords: cornea: epithelium • wound healing 
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