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

Carrington, Louise Mary, Albon, Julie, Anderson, Ian, Kamma-Lorger, Christina S. and Boulton, Michael Edwin 2006. Differential regulation of key stages in early corneal wound healing by TGF-beta isoforms and their inhibitors. Investigative Ophthalmology and Visual Science 47 (5) , pp. 1886-1894. 10.1167/iovs.05-0635

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Abstract

PURPOSE: Inhibition of TGF-beta reduces myofibroblast differentiation and fibrosis in the cornea. Determining the actions of distinct TGF-beta 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-beta1, -beta2, and -beta3; IL-10; and neutralizing human monoclonal antibodies (mAbs) against TGF-beta1 (CAT-192) or -beta2, (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 (alpha-smooth muscle actin) between 0 and 5 days. RESULTS: TGF-beta1 delayed re-epithelialization, increased repopulation of the stroma, increased keratocyte proliferation and was the only isoform to promote myofibroblast differentiation. The anti-TGF-beta1 mAb, CAT-192 promoted re-epithelialization and reduced repopulation of the stroma. Exogenous TGF-beta3 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-beta2 or the anti-TGF-beta2 mAb, CAT-152 had little effect on any repair parameter. CONCLUSIONS: The results confirm TGF-beta1 as the principal isoform in corneal wound healing and suggest that inhibition of the action of TGF-beta1 can promote corneal wound healing. Treatment with the anti-TGF-beta1 mAb CAT-192 accelerates corneal re-epithelialization but reduces cell repopulation of the stroma. The cytokines TGF-beta3 and IL-10 have opposing actions to that of TGF-beta1.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Optometry and Vision Sciences
Additional Information: Confirmation received by publisher on 21 February 2014 that publisher's pdf can be self-archived 6 months after publication.
Publisher: Association for Research in Vision and Ophthalmology
ISSN: 0146-0404
Date of First Compliant Deposit: 30 March 2016
Last Modified: 04 Jun 2017 01:36
URI: http://orca.cf.ac.uk/id/eprint/846

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