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MMP‐2 and MMP‐9 synergize in promoting choroidal neovascularization
Author(s) -
Lambert Vincent,
Wielockx Ben,
Munaut Carine,
Galopin Catherine,
Jost Maud,
Itoh Takeshi,
Werb Zena,
Baker Andrew,
Libert Claude,
Krell Hans-Willi,
Foidart Jean-Michel,
Noël Agnès,
Rakic Jean-Marie
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.03-0113fje
Subject(s) - choroidal neovascularization , matrix metalloproteinase , macular degeneration , neovascularization , gelatinase , gelatinase a , matrix metalloproteinase inhibitor , endogeny , tissue inhibitor of metalloproteinase , medicine , cancer research , chemistry , angiogenesis , immunology , ophthalmology
Matrix metalloproteinase 2 (MMP‐2) and MMP‐9 are increased in human choroidal neovascularization (CNV) occurring during the exudative most aggressive form of age‐related macular degeneration (AMD), but their precise role and potential interactions remain unclear. To address the question of MMP‐2 and MMP‐9 functions, mice deficient in the expression of MMP‐ 2 (MMP‐2 KO), MMP‐9 (MMP‐9 KO), and both MMP‐2 and MMP‐9 (MMP‐2,9 KO) with their corresponding wild‐type mice (WT) underwent CNV induction by laser‐induced rupture of the Bruch's membrane. Both the incidence and the severity of CNV were strongly attenuated in double deficient compared with single gene deficient mice or corresponding WT controls. The reduced neovascularization was accompanied by fibrinogen/fibrin accumulation. Furthermore, overexpression of the endogenous MMP inhibitors TIMP‐1 or TIMP‐2 (delivered by adenoviral vectors) in WT mice or daily injection of a synthetic and gelatinase selective MMP inhibitor (Ro 26‐2853) significantly decreased the pathological reaction. These findings suggest that MMP‐2 and MMP‐9 may cooperate in the development of AMD and that their selective inhibition represents an alternative strategy for the treatment of choroidal neovascularization.