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MMP-2 and MMP-9 synergize in promoting choroidal neovascularization.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Lambert, Vincent Wielockx, Ben Munaut, Carine Galopin, Catherine Jost, Maud Itoh, Takeshi Werb, Zena Baker, Andrew Libert, Claude Krell, H. L. Foidart, J. -M. Noël, Agnés Rakic, J. M. |
| Copyright Year | 2003 |
| 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. |
| Starting Page | 789 |
| Ending Page | 797 |
| Page Count | 9 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://orbi.ulg.ac.be/bitstream/2268/26522/1/lambert%20MMP2-9%20FASEBJE%202003.pdf |
| Alternate Webpage(s) | http://orbi.ulg.ac.be/bitstream/2268/26522/2/lambert%20MMP2-9%20FASEBJEon%20line%202003.pdf |
| PubMed reference number | 14563686v1 |
| Volume Number | 17 |
| Issue Number | 15 |
| Journal | FASEB journal : official publication of the Federation of American Societies for Experimental Biology |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adenoviruses Choroidal Neovascularization Copy Number Polymorphism Gelatinases Macular degeneration Matrix Metalloproteinases Metalloproteases Pathologic Neovascularization Promotion (action) Rupture Serotonin Uptake Inhibitors Tissue membrane antileukoprotease |
| Content Type | Text |
| Resource Type | Article |
