September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
Role of Epidermal Growth Factor Receptor and Src-Family Kinase Activation in Human Corneal Epithelial Wound Healing
Author Affiliations & Notes
  • Hasan Masud Bashir
    Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Hiroshi Maeno
    Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Christine Marshall
    Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Claire Heesun Park
    Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Richu Raju
    Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • John T Seykora
    Department of Dermatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Vivian Lee
    Department of Ophthalmology, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States
  • Footnotes
    Commercial Relationships   Hasan Bashir, None; Hiroshi Maeno, None; Christine Marshall, None; Claire Park, None; Richu Raju, None; John Seykora, Galderma (F), Myriad Genetics (C), Novartis (F), PIQUR Therapeutics AG (F), Rohto Pharmaceutical Co. (F); Vivian Lee, None
  • Footnotes
    Support  1K08EY025742-01, K12EY015398, Research to Prevent Blindness Unrestricted Departmental Grant
Investigative Ophthalmology & Visual Science September 2016, Vol.57, 1281. doi:
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      Hasan Masud Bashir, Hiroshi Maeno, Christine Marshall, Claire Heesun Park, Richu Raju, John T Seykora, Vivian Lee; Role of Epidermal Growth Factor Receptor and Src-Family Kinase Activation in Human Corneal Epithelial Wound Healing. Invest. Ophthalmol. Vis. Sci. 2016;57(12):1281.

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      © 2017 Association for Research in Vision and Ophthalmology.

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Abstract

Purpose : Corneal epithelial wounds are a serious global concern that can lead to deeper corneal scarring and blindness. Our previous study suggests activation of epidermal growth factor receptor (EGFR) and Src-family kinases (SFK) may play a role in corneal epithelial wound healing in murine derived corneal epithelial cells. To further understand the role of the EGFR/SFK pathway in wound healing, wound assays using immortalized human corneal epithelial cells and primary human corneal epithelial cells were examined in the presence and absence of tyrosine kinase inhibitors. Using live cell imaging and Western blot analysis, cellular events were correlated to cell migration rates.

Methods : Monolayers derived from 2.040 pRSV-T ATCC (2.040) immortalized cells and primary human corneal epithelial cells (HCEC) were established and subsequently wounded. Cells were incubated with small molecule tyrosine kinase inhibitors or vehicle at various concentrations in pairs. Wound assays were either imaged with a live cell imaging system and analyzed with Image J software, or collected as protein lysates 24 hours after wounding for Western blot analysis.

Results : Cells incubated with tyrosine kinase inhibitors showed marked inhibition of cell migration into the wound gaps 24 hours post wounding at all concentrations tested, while cells with vehicle only demonstrated near complete resolution of the wound area. There was a strong correlation between cell migration and activation of EGFR and SFKs. Treatment with tyrosine kinase inhibitors inhibited cell migration and this correlated with decreased levels of activated EGFR and SFK in wounded 2.040 and HCEC.

Conclusions : Enhanced corneal epithelial wound healing was previously observed in murine derived corneal epithelial cells with increased levels of activated EGFR and SFK. The introduction of small molecule tyrosine kinase inhibitors inhibited the capacity of wounded human corneal epithelial cells to migrate and close wounds, paralleling decreased activation of EGFR and SFK on Western blot. Results from this study suggest a critical role for EGFR and SFK activation in human corneal epithelial wound healing with small molecule tyrosine kinase inhibitors potentiating EGFR/SFK dependent signaling. Further studies to enhance human corneal epithelial wound healing through increased activation of EGFR and SFK should be conducted.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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