Differences in the TGF-{beta}1-induced profibrotic response of anterior and posterior corneal keratocytes in vitro

Invest Ophthalmol Vis Sci. 2010 Apr;51(4):1935-42. doi: 10.1167/iovs.09-3823. Epub 2009 Nov 11.

Abstract

Purpose. To characterize phenotypic differences between anterior and posterior corneal keratocytes after stimulation with the profibrotic agent transforming growth factor-beta1 (TGF-beta1) in vitro. Methods. Sixteen corneas from healthy felines were obtained immediately after death. Lamellar dissection was performed to separate the anterior and posterior stroma at approximately 50% depth either manually (n = 2) or with a Moria microkeratome (300-mum head; n = 14). Cells from the anterior and posterior stroma were cultured separately but under identical conditions. Using immunohistochemistry and Western blot techniques, Ki-67 staining and relative expression of Thy-1, alpha smooth muscle actin (alpha-SMA), and fibronectin were assessed after stimulation with different TGF-beta1 concentrations. In addition, anterior and posterior cells cultured in different concentrations of TGF-beta1 were wounded with a razor blade, and the wound area and time to closure were determined. Results. Stimulation by all concentrations of TGF-beta1 increased the proportion of Ki-67-positive cells in anterior and posterior cell cultures, but this increase was noted earlier in posterior cells than in anterior cells. Increasing TGF-beta1 concentration also increased the relative expression of Thy-1, alpha-SMA, and fibronectin in anterior and posterior fibroblasts. However, anterior cells expressed these fibrotic markers at lower TGF-beta1 concentrations than did posterior keratocytes. After mechanical wounding, posterior cells closed the wound area faster than did anterior cells at all concentrations of TGF-beta1. Conclusions. The present experiments show that anterior and posterior corneal keratocytes exhibit different sensitivities to the profibrotic growth factor TGF-beta1. This heterogeneity of keratocyte response may impact wound closure after mechanical wounding.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Actins / metabolism
  • Animals
  • Blotting, Western
  • Cats
  • Cells, Cultured
  • Corneal Injuries
  • Corneal Stroma / cytology
  • Corneal Stroma / drug effects*
  • Corneal Stroma / metabolism
  • Fibroblasts / drug effects*
  • Fibroblasts / metabolism
  • Fibronectins / metabolism
  • Immunohistochemistry
  • Ki-67 Antigen / metabolism
  • Phenotype
  • Thy-1 Antigens / metabolism
  • Transforming Growth Factor beta1 / pharmacology*

Substances

  • Actins
  • Fibronectins
  • Ki-67 Antigen
  • Thy-1 Antigens
  • Transforming Growth Factor beta1