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The Epidermal Growth Factor Receptor (EGFR): Role in Corneal Wound Healing and Homeostasis

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Abstract

To evaluate the role of the epidermal growth factor receptor (EGFR) in corneal epithelial wound healing, the effect of an EGFR inhibitor on epithelial cell proliferation and cell stratification during wound healing was investigated. From 3 days prior to wounding until wound healing was complete, rats were systemically treated with either an EGFR tyrosine kinase inhibitor (ZD1839) at 40 mg kg−1 day−1or 80 mg kg−1 day−1, or with vehicle only (control). A single corneal wound was made in the center of 66 rat corneas, using a 6.0 mm glass tube wrapped in tissue paper soaked in n-heptanol. Subsequently, each wound was photographed and measured by a computer-assisted digitizer every 12 hr. To determine the number of cells in S phase, entire corneas were labelled with3H-thymidine and subjected to autoradiography at 0, 12, 24 and 48 hr after wounding. Epithelial thickness was also measured at these time points by microscopy. Epithelial wound healing was significantly and dose-dependently delayed following administration of ZD1839. At 24 hr after wounding, the number of S-phase cells in the limbal corneal epithelium was significantly lower in both the treated groups compared with the control group (P < 0.05). In the cornea before wounding (0 hr) and at 48 hr post-wounding, epithelial thickness was also significantly less in treated rats compared with controls (P < 0.05). These results indicate that EGFR inhibition affects epithelial cell proliferation and stratification during corneal epithelial wound healing and may play a role in maintaining normal corneal epithelial thickness.

References (33)

  • S. Higashiyama et al.

    A heparin-binding growth factor secreted by macrophage-like cells that is related to EGF

    Science

    (1991)
  • S. Kasayama et al.

    Expression of the epidermal growth factor gene in mouse lachrymal gland: comparison with that in the submandibular gland and kidney

    J. Mol. Endocrinol.

    (1990)
  • P.T. Khaw et al.

    Detection of transforming growth factor-α messenger RNA and protein in human corneal epithelial cells

    Invest. Ophthalmol. Vis. Sci.

    (1992)
  • S. Kinoshita

    Clinical application of epidermal growth factor in ocular surface disorders

    J. Dermatol.

    (1992)
  • T. Kitazawa et al.

    The mechanism of accelerated corneal epithelial healing by human epidermal growth factor

    Invest. Ophthalmol. Vis. Sci.

    (1990)
  • R.M. Lavker et al.

    Relative proliferative rates of limbal and corneal epithelia

    Invest. Ophthalmol. Vis. Sci.

    (1991)
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    Address correspondence to: Yo Nakamura, Department of Ophthalmology, Kyoto Prefectural University of Medicine, 465 Kajiicho, Hirokoji-agaru, Kawaramachi-dori, Kamigyo-ku, Kyoto 602-0841, Japan. E-mail: [email protected]

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