Differential regulation of key stages in early corneal wound healing by TGF-β isoforms and their inhibitors

Louise M. Carrington, Julie Albon, Ian Anderson, Christina Kamma, Mike Boulton

Research output: Contribution to journalArticlepeer-review

83 Scopus citations

Abstract

PURPOSE. Inhibition of TGF-β reduces myofibroblast differentiation and fibrosis in the cornea. Determining the actions of distinct TGF-β isoforms and their inhibitors during early corneal wound healing is an essential step in guiding therapeutic intervention. METHODS. Bovine serum-free corneal cell and wounded organ cultures were challenged with a range of concentrations of TGF-β1, -β2, and -β3; IL-10; and neutralizing human monoclonal antibodies (mAbs) against TGF-β1 (CAT-192) or -β2, (CAT-152). Cultures were assessed for re-epithelialization, proliferation (cell counts and cresyl violet assay), morphology (histologic examination), repopulation of the area under the wound, and myofibroblast transformation (α-smooth muscle actin) between 0 and 5 days. RESULTS. TGF-β1 delayed re-epithelialization, increased repopulation of the stroma, increased keratocyte proliferation and was the only isoform to promote myofibroblast differentiation. The anti-TGF-β1 mAb, CAT-192 promoted re-epithelialization and reduced repopulation of the stroma. Exogenous TGF-β3 had little effect on re-epithelialization but reduced repopulation of the stroma. IL-10 promoted corneal re-epithelialization at low doses but inhibited this response at high doses. Stromal repopulation was prevented by all doses of IL-10. TGF-β2 or the anti-TGF-β2 mAb, CAT-152 had little effect on any repair parameter. CONCLUSIONS. The results confirm TGF-β1 as the principal isoform in corneal wound healing and suggest that inhibition of the action of TGF-β1 can promote corneal wound healing. Treatment with the anti-TGF-β1 mAb CAT-192 accelerates corneal re-epithelialization but reduces cell repopulation of the stroma. The cytokines TGF-β3 and IL-10 have opposing actions to that of TGF-β1.

Original languageEnglish (US)
Pages (from-to)1886-1894
Number of pages9
JournalInvestigative Ophthalmology and Visual Science
Volume47
Issue number5
DOIs
StatePublished - May 2006

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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