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Louise M. Carrington, Julie Albon, Ian Anderson, Christina Kamma, Mike Boulton; Differential Regulation of Key Stages in Early Corneal Wound Healing by TGF-β Isoforms and Their Inhibitors. Invest. Ophthalmol. Vis. Sci. 2006;47(5):1886-1894. doi: 10.1167/iovs.05-0635.
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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.
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