Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization.
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.
Lecomte
Julie
J
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.
Louis
Krystel
K
Detry
Benoit
B
Blacher
Silvia
S
Lambert
Vincent
V
Bekaert
Sandrine
S
Munaut
Carine
C
Paupert
Jenny
J
Blaise
Pierre
P
Foidart
Jean-Michel
JM
Rakic
Jean-Marie
JM
Krane
Stephen M
SM
Noel
Agnès
A
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
D053509:Matrix Metalloproteinase 13