title: MMP-2 and MMP-9 synergize in promoting choroidal neovascularization.
abstract: 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.
authors.affiliation: Laboratory of Tumor and Development Biology, University of Liège, Belgium.
authors.forename: Vincent
authors.initials: V
authors.lastname: Lambert
authors.forename: Ben
authors.initials: B
authors.lastname: Wielockx
authors.forename: Carine
authors.initials: C
authors.lastname: Munaut
authors.forename: Catherine
authors.initials: C
authors.lastname: Galopin
authors.forename: Maud
authors.initials: M
authors.lastname: Jost
authors.forename: Takeshi
authors.initials: T
authors.lastname: Itoh
authors.forename: Zena
authors.initials: Z
authors.lastname: Werb
authors.forename: Andrew
authors.initials: A
authors.lastname: Baker
authors.forename: Claude
authors.initials: C
authors.lastname: Libert
authors.forename: Hans-Willi
authors.initials: HW
authors.lastname: Krell
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Foidart
authors.forename: Agnès
authors.initials: A
authors.lastname: Noël
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Rakic
mesh_terms: D000818:Animals; D002829:Choroid / Q000737:chemistry / Q000201:enzymology* / Q000473:pathology; D020256:Choroidal Neovascularization / Q000201:enzymology / Q000209:etiology* / Q000473:pathology; D005337:Fibrin / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D005786:Gene Expression Regulation; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000502:physiology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000502:physiology*; D061965:Matrix Metalloproteinase Inhibitors; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D011480:Protease Inhibitors / Q000494:pharmacology
chemical_list: D061965:Matrix Metalloproteinase Inhibitors; D011480:Protease Inhibitors; D005337:Fibrin; D005340:Fibrinogen; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9