title: Matrix metalloproteinase 14 overexpression reduces corneal scarring.
abstract: 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.
authors.affiliation: INSERM U563, Toulouse, France.
authors.forename: S D
authors.initials: SD
authors.lastname: Galiacy
authors.forename: P
authors.initials: P
authors.lastname: Fournié
authors.forename: D
authors.initials: D
authors.lastname: Massoudi
authors.forename: E
authors.initials: E
authors.lastname: Ancèle
authors.forename: J-C
authors.initials: JC
authors.lastname: Quintyn
authors.forename: A
authors.initials: A
authors.lastname: Erraud
authors.forename: I
authors.initials: I
authors.lastname: Raymond-Letron
authors.forename: F
authors.initials: F
authors.lastname: Rolling
authors.forename: F
authors.initials: F
authors.lastname: Malecaze
mesh_terms: D000818:Animals; D002921:Cicatrix / Q000628:therapy*; D003315:Cornea / Q000473:pathology*; D003318:Corneal Opacity / Q000628:therapy; D000229:Dependovirus / Q000235:genetics; D005260:Female; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D053511:Matrix Metalloproteinase 14 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D015854:Up-Regulation; D014945:Wound Healing
chemical_list: C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14