Therapeutic effects of adenoviral gene transfer of bone morphogenic proteinalkali injury model in mice

An alkali burn in the cornea is a common serious clinical problem often leading to permanent visual impairment. Since transforming growth factor-beta (TGF-beta) is involved in the response to corneal injury, we evaluated the therapeutic effects of adenoviral gene transfer of mouse bone morphogenic proten-7 (BMP-7), which has antagonistic effects on TGF-beta in tissue fibrosis. Burned cornea did not express endogenous BMP-7 mRNA and protein. Resurfacing of the burned cornea by invading conjunctival epithelium was accelerated by adenoviral introduction of BMP-7. Exogenous BMP- 7 expression also suppressed myofibroblast generation, appearance of monocytes/macrophages and expression of MCP-1, TGF-beta s, and collagen I alpha 2 chain in the affected stroma. Ectopic BMP- 7 did not suppress stromal neovascularization throughout the interval studied and also did not reduce VEGF mRNA expression at Day 10. Ectopic BMP- 7 in burned corneal tissue resulted in activation of Smad1/5/8 signaling and partial suppression of the phospho-Smad2 signal. These data suggest that overexpression of BMP- 7 is an effective strategy for treatment of ocular alkali burns.