MMP‐2 and MMP‐9 synergize in promoting choroidal neovascularization
2003; Wiley; Volume: 17; Issue: 15 Linguagem: Inglês
10.1096/fj.03-0113fje
ISSN1530-6860
AutoresVincent Lambert, Ben Wielockx, Carine Munaut, Catherine Galopin, Maud Jost, Takeshi Itoh, Zena Werb, Andrew H. Baker, Claude Libert, Hans‐Willi Krell, Jean-Michel Foidart, Agnès Noël, Jean‐Marie Rakic,
Tópico(s)Retinal Imaging and Analysis
ResumoMatrix 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.
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