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Pierre R. Fournie, Stéphane Galiacy, Massoudi Dawiyat, Angélique Erraud, Isabelle Raymond-Letron, Fabienne Rolling, François Malecaze; Matrix Metalloproteinase 14 Overexpression Reduces Corneal Scarring. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1986.
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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) remodeling. 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 synthesize a new ECM, mainly composed of type III collagen. This scar tissue is less organized than the regular stroma, thus explaining corneal opacity. ECM remodeling 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 Metalloproteinase family. We hypothesized that its overexpression in the corneal stroma during wound repair will increase ECM remodeling and thus prevent collagen deposition in the scar tissue.
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 characterized several parameters: clinical observation, histology, and wound healing markers.
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. We observed that MMP14 overexpression reduced corneal opacity. Our preliminary results showed a decreased in edema and corneal scar formation, associated with a decreased expression of alpha smooth actin and type III collagen.
These results represent proof of concept that gene transfer of MMP14 can reduce scar formation, which could have therapeutic applications after corneal trauma.
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