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  • Original Article
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Matrix metalloproteinase 14 overexpression reduces corneal scarring

Gene Therapy volume 18, pages 462–468 (2011)Cite this article

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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.

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Acknowledgements

We thank M Allouche and B Couderc for helpful comments and critical reading. This work was supported by the Fondation de l’Avenir (study ET7-474), la Fondation de France (grants ‘Berthe Fouassier’: 2008002176, 2009002318 and 2009002320), the Laboratoires Pierre Fabre and the INSERM. We also thank MA Daussion and J Bernaud from the Centre de Recherche de Chirurgie Expérimentale Claude Bernard (CHU Purpan, Toulouse, France) for animal care and experiments.

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Author notes

  1. S D Galiacy and P Fournié: These authors contributed equally to this work.

Authors and Affiliations

  1. INSERM U563, Toulouse, France

    S D Galiacy, P Fournié, D Massoudi, E Ancèle, J-C Quintyn, A Erraud, I Raymond-Letron & F Malecaze

  2. Université Toulouse III Paul Sabatier, Centre de Physiopathologie de Toulouse Purpan, Toulouse, France

    S D Galiacy, P Fournié, D Massoudi, E Ancèle, J-C Quintyn, A Erraud & F Malecaze

  3. CHU Toulouse, Hôpital Purpan, Service d’Ophtalmologie, Toulouse, France

    P Fournié, E Ancèle, J-C Quintyn & F Malecaze

  4. Département de Pathologie, Ecole Nationale Vétérinaire de Toulouse, Toulouse, France

    I Raymond-Letron

  5. Laboratoire de Thérapie Génique, INSERM UMR U649, Institut de Recherche Thérapeutique 1, Université de Nantes, Nantes, France

    F Rolling

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  1. S D Galiacy
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Correspondence to P Fournié.

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Galiacy, S., Fournié, P., Massoudi, D. et al. Matrix metalloproteinase 14 overexpression reduces corneal scarring. Gene Ther 18, 462–468 (2011). https://doi.org/10.1038/gt.2010.159

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