title: Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization.
abstract: 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.
authors.affiliation: Laboratory of Tumor and Developmental Biology, Tour de Pathologie, CHU (B23), Groupe Interdisciplinaire de Génoprotéomique Appliquée-Research (GIGA-Cancer), University of Liege, 4000, Liege, Belgium.
authors.forename: Julie
authors.initials: J
authors.lastname: Lecomte
authors.forename: Krystel
authors.initials: K
authors.lastname: Louis
authors.forename: Benoit
authors.initials: B
authors.lastname: Detry
authors.forename: Silvia
authors.initials: S
authors.lastname: Blacher
authors.forename: Vincent
authors.initials: V
authors.lastname: Lambert
authors.forename: Sandrine
authors.initials: S
authors.lastname: Bekaert
authors.forename: Carine
authors.initials: C
authors.lastname: Munaut
authors.forename: Jenny
authors.initials: J
authors.lastname: Paupert
authors.forename: Pierre
authors.initials: P
authors.lastname: Blaise
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Rakic
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Krane
authors.forename: Agnès
authors.initials: A
authors.lastname: Noel
mesh_terms: D000818:Animals; D020256:Choroidal Neovascularization / Q000201:enzymology* / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D017353:Gene Deletion; D015870:Gene Expression; D006801:Humans; D008268:Macular Degeneration / Q000201:enzymology* / Q000235:genetics; D053509:Matrix Metalloproteinase 13 / Q000235:genetics / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D053509:Matrix Metalloproteinase 13