Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization
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In this study, we evaluate the potential involvement of collagenase-3 (MMP13), a matrix metalloproteinase (MMP) family member, in the exudative form of age-related macular degeneration characterized by a neovascularisation into the choroid. RT-PCR analysis revealed that human neovascular membranes issued from patients with AMD expressed high levels of Mmp13. The contribution of MMP13 in choroidal neovascularization (CNV) formation was explored by using a murine model of laser-induced CNV and applying it to wild-type mice (WT) and Mmp13-deficient mice (Mmp13 −/− mice). Angiogenic and inflammatory reactions were explored by immunohistochemistry. The implication of bone marrow (BM)-derived cells was determined by BM engraftment into irradiated mice and by injecting mesenchymal stem cells (MSC) isolated from WT BM. The deficiency of Mmp13 impaired CNV formation which was fully restored by WT BM engraftment and partially rescued by several injections of WT MSC. The present study sheds light on a novel function of MMP13 during BM-dependent choroidal vascularization and provides evidence for a role for MSC in the pathogenesis of CNV.
KeywordsCNV MMP13 Angiogenesis Bone marrow Mesenchymal stem cells
Age-related macular degeneration
Mesenchymal stem cells
Retinal pigmented epithelium
Tissue inhibitor of metalloprotease
The authors acknowledge P. Gavitelli, F. Olivier, M.-R. Pignon, E. Feyereisen, L. Poma, G. Roland and N. Lefin for collaboration and technical assistance. They thank the GIGA imaging and flow cytometry platform for their help. This work was supported by grants from the European Union Framework Program projects (FP7, MICROENVIMET), the Fonds de la Recherche Scientifique Médicale, the Fonds National de la Recherche Scientifique (F.N.R.S., Belgium), the Federation belge contre le Cancer, the Fonds spéciaux de la Recherche (University of Liège), the Centre Anticancéreux près l’Université de Liège, the Fonds Léon Fredericq (University of Liège), the D.G.T.R.E. from the “Région Wallonne” the Interuniversity Attraction Poles Program-Belgian Science Policy (Brussels, Belgium). JL is recipient of a Televie-FNRS grant. SMK was supported by a grant from the US National Institutes of Health.
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