Matrix metalloproteinase 14 overexpression reduces corneal scarring

Gene Ther. 2011 May;18(5):462-8. doi: 10.1038/gt.2010.159. Epub 2010 Dec 16.


Once a corneal scar develops, surgical management remains the only option for visual rehabilitation. Corneal transplantation is the definitive treatment for a corneal scar. In addition to the challenges posed by graft rejections and other postoperative complications, the lack of high-quality donor corneas can limit the benefits possible with keratoplasty. The purpose of our study was to evaluate a new therapeutic strategy for treating corneal scarring by targeting collagen deposition. We overexpressed a fibril collagenase (matrix metalloproteinase 14 (MMP14)) to prevent collagen deposition in the scar tissue. We demonstrated that a single and simple direct injection of recombinant adeno-associated virus-based vector expressing murine MMP14 can modulate gene expression of murine stromal keratocytes. This tool opens new possibilities with regard to treatment. In a mouse model of corneal full-thickness incision, we observed that MMP14 overexpression reduced corneal opacity and expression of the major genes involved in corneal scarring, especially type III collagen and α-smooth muscle actin. These results represent proof of concept that gene transfer of MMP14 can reduce scar formation, which could have therapeutic applications after corneal trauma.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cicatrix / therapy*
  • Cornea / pathology*
  • Corneal Opacity / therapy
  • Dependovirus / genetics
  • Female
  • Gene Transfer Techniques*
  • Genetic Vectors
  • Matrix Metalloproteinase 14 / genetics*
  • Matrix Metalloproteinase 14 / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Up-Regulation
  • Wound Healing


  • MMP14 protein, human
  • Matrix Metalloproteinase 14