Cellular and Molecular Life Sciences

, Volume 68, Issue 4, pp 677–686

Bone marrow-derived mesenchymal cells and MMP13 contribute to experimental choroidal neovascularization

  • Julie Lecomte
  • Krystel Louis
  • Benoit Detry
  • Silvia Blacher
  • Vincent Lambert
  • Sandrine Bekaert
  • Carine Munaut
  • Jenny Paupert
  • Pierre Blaise
  • Jean-Michel Foidart
  • Jean-Marie Rakic
  • Stephen M. Krane
  • Agnès Noel
Research Article

DOI: 10.1007/s00018-010-0476-6

Cite this article as:
Lecomte, J., Louis, K., Detry, B. et al. Cell. Mol. Life Sci. (2011) 68: 677. doi:10.1007/s00018-010-0476-6

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.

Keywords

CNVMMP13AngiogenesisBone marrowMesenchymal stem cells

Abbreviations

AMD

Age-related macular degeneration

BM

Bone marrow

CAM

Choroiallantoic membrane

CNV

Choroidal neovascularization

MSC

Mesenchymal stem cells

RPE

Retinal pigmented epithelium

TIMP

Tissue inhibitor of metalloprotease

Copyright information

© Springer Basel AG 2010

Authors and Affiliations

  • Julie Lecomte
    • 1
  • Krystel Louis
    • 1
  • Benoit Detry
    • 1
  • Silvia Blacher
    • 1
  • Vincent Lambert
    • 1
    • 2
  • Sandrine Bekaert
    • 1
  • Carine Munaut
    • 1
  • Jenny Paupert
    • 1
  • Pierre Blaise
    • 2
  • Jean-Michel Foidart
    • 1
  • Jean-Marie Rakic
    • 2
  • Stephen M. Krane
    • 3
  • Agnès Noel
    • 1
  1. 1.Laboratory of Tumor and Developmental Biology, Tour de Pathologie, CHU (B23), Groupe Interdisciplinaire de Génoprotéomique Appliquée-Research (GIGA-Cancer)University of LiegeLiegeBelgium
  2. 2.Department of OphthalmologyCHULiegeBelgium
  3. 3.Department of Medicine, Center for Immunology and Inflammatory DiseaseHarvard Medical School and Massachusetts General HospitalBostonUSA