Effects of transforming growth factor beta on corneal epithelial and stromal cell function in a rat wound healing model after excimer laser keratectomy

Graefes Arch Clin Exp Ophthalmol. 1998 Nov;236(11):834-43. doi: 10.1007/s004170050168.

Abstract

Background: Transforming growth factor beta (TGF-beta) regulates extracellular matrix deposition, cell proliferation, and migration, and is expressed in cornea. TGF-beta is thought to be involved in the corneal wound healing process.

Methods: The central corneal area (3 mm in diameter) of Lewis rats was ablated using PTK mode excimer laser and the wound healing process was observed at 12 and 24 h and 2, 5, 10, and 30 days after treatment. The expression of TGF-beta 1, -beta 2 and -beta 3, TGF-beta type I and type II receptors, alpha 3, alpha 5, beta 4 integrin subunits, laminin and fibronectin was studied immunohistochemically. Antibody neutralizing TGF-beta 1, -beta 2 and -beta 3 was administered intraperitoneally, 50 micrograms daily, for 5 days after the laser treatment to investigate the effects of TGF-beta function blockade.

Results: At the leading edge of the regenerating epithelium, no TGF-beta type I and type II receptors and beta 4 integrin subunits were expressed after 24 h. Regenerating epithelium covered the ablated area after 2 days. An abnormal fibrotic layer was formed in the subepithelial area. This layer contained round-shaped cells in the stroma in the early stage (2-5 days after laser ablation) and spindle-shaped fibroblast-like keratocytes after 10 days. Laminin and fibronectin expression increased in the fibrotic layer. The increased stromal cells expressed TGF-beta isoforms and TGF-beta receptors. Neutralizing TGF-beta inhibited the stromal cell increase in the laser ablated area after 5 days.

Conclusion: TGF-beta may be involved in epithelial cell migration and stromal cell reaction during the corneal wound healing process after excimer laser ablation in rat models.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activin Receptors, Type I*
  • Animals
  • Cell Movement
  • Cornea / surgery
  • Corneal Stroma / physiology*
  • Epithelium, Corneal / physiology*
  • Fibronectins / metabolism
  • Immunoenzyme Techniques
  • Immunoglobulins / administration & dosage
  • Injections, Intraperitoneal
  • Integrins / metabolism
  • Laminin / metabolism
  • Lasers, Excimer
  • Photorefractive Keratectomy*
  • Protein Serine-Threonine Kinases / metabolism
  • Rats
  • Rats, Inbred Lew
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Receptors, Transforming Growth Factor beta / metabolism
  • Transforming Growth Factor beta / immunology
  • Transforming Growth Factor beta / physiology*
  • Wound Healing* / physiology

Substances

  • Fibronectins
  • Immunoglobulins
  • Integrins
  • Laminin
  • Receptors, Transforming Growth Factor beta
  • Transforming Growth Factor beta
  • Protein Serine-Threonine Kinases
  • Activin Receptors, Type I
  • Receptor, Transforming Growth Factor-beta Type I
  • Receptor, Transforming Growth Factor-beta Type II
  • Tgfbr1 protein, rat