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Matrix metalloproteinase 14 overexpression reduces corneal scarring
Author(s) -
GALIACY S,
FOURNIE P,
MASSOUDI D,
ANCELE E,
QUINTYN JC,
ERRAUD A,
RAYMONDLETRON I,
ROLLING F,
MALECAZE F
Publication year - 2010
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2010.4135.x
Subject(s) - extracellular matrix , myofibroblast , wound healing , matrix metalloproteinase , fibroblast , stroma , fibrosis , fibrocyte , type i collagen , pathology , collagenase , cornea , microbiology and biotechnology , medicine , chemistry , ophthalmology , immunology , biology , immunohistochemistry , in vitro , biochemistry , enzyme
Purpose Corneal wound healing is an everyday preoccupation for ophthalmologists.Corneal transparency depends on the scarring quality after a traumatic corneal wound, but also after refractive corneal surgery. Cicatrisation and fibrosis formation involve epithelial/fibroblast interactions via paracrin signals inducing extracellular matrix (ECM) remodelling. The major event is fibroblast activation and differentiation into myofibroblasts. These cells have a key role in the fibrotic response. They acquire contractile properties, and synthetise a new ECM, mainly composed of type III collagen. This scar tissue is less organised than the regular stroma, thus explaining corneal opacity. ECM remodelling is a critical step which aims to digest the excess of ECM by proteolysis of type III collagen. MMP14 is a membrane‐bound fibrillar collagenase from the Matrix Metalloprotease family. We hypothesised that its overexpression in the corneal stroma during wound repair will increase ECM remodelling and thus prevent collagen deposition in the scar tissue. Methods We developed an adeno‐associated virus‐based vector expressing murine MMP14 under the control of the CMV promoter. We evaluated MMP14 overexpression after viral transfection in a murine model of corneal wound healing. We characterised several parameters: clinical observation, histology, and wound healing markers. Results Our preliminary results showed a decreased in oedema and corneal scar formation, associated with a decreased expression of alpha smooth actin and type III collagen. Conclusion These results represent proof of concept that gene transfer of MMP14 can reduce scar formation, which could have therapeutic applications after corneal trauma.