Therapeutic effects of adenoviral gene transfer of bone morphogenic protein-7 on a corneal alkali injury model in mice

Lab Invest. 2005 Apr;85(4):474-86. doi: 10.1038/labinvest.3700247.

Abstract

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 protein-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-betas, and collagen I alpha2 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenoviridae / genetics*
  • Animals
  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins / genetics*
  • Cell Division
  • Corneal Diseases / pathology
  • Corneal Diseases / therapy*
  • DNA-Binding Proteins / metabolism
  • Disease Models, Animal
  • Eye Injuries / pathology
  • Eye Injuries / therapy*
  • Gene Transfer Techniques*
  • Immunohistochemistry
  • Mice
  • Mice, Inbred C57BL
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Smad Proteins
  • Smad1 Protein
  • Trans-Activators / metabolism
  • Transforming Growth Factor beta / genetics*

Substances

  • Bone Morphogenetic Protein 7
  • Bone Morphogenetic Proteins
  • DNA-Binding Proteins
  • RNA, Messenger
  • Smad Proteins
  • Smad1 Protein
  • Smad1 protein, mouse
  • Trans-Activators
  • Transforming Growth Factor beta