Matrix metalloproteinase (MMP) expression in experimental choroidal neovascularization

Purpose. Matrix metalloproteinases (MMP) are a family of proteolytic enzyme s that degrade basement membrane and extracellular matrix proteins. To gain information on the possible role of MMPs in choroidal neovascularization ( CNV), we have analyzed the mRNA expression of MMP-2 and MMP-9, two forms of MMPs implicated in ocular neovascularization, in a rat model. Methods. Choroidal neovascularization was induced in pigmented rats by kryp ton laser photocoagulation of the fundus whereafter eyes were enucleated at 1, 3, 5, 7, 10 and 60 days. Antisense and sense riboprobes were generated using DNA complementary to MMP-2 and MMP-9, and mRNA expression was analyze d using in situ hybridization. Results. In the untreated eyes MMP-2 mRNA expression was weakly detected in cells within the choroid. In laser-treated eyes MMP-2 mRNA expression was markedly increased and mainly localized to macrophage-like and retinal pigm ent epithelial (RPE)-like cells invading the choroid, subretinal space and inner retina. This increase in MMP-2 mRNA expression peaked at day 10 where after a decline was detected. MMP-9 mRNA expression was low in untreated ey es and did not increase following laser treatment. Conclusion. The results show that MMP-2 mRNA expression is increased in exp erimental CNV, and support of a role for MMP-2 in the development of CNV in age-related macular degeneration.