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Matrix metalloproteinase (MMP) expression in experimental choroidal neovascularization
1Department of Ophthalmology, St. Erik's Eye Hospital, Karolinska Institutet, Stockholm, Sweden. ankvanta@swipnet.se
Purpose:
Matrix metalloproteinases (MMP) are a family of proteolytic enzymes 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 krypton 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 analyzed 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 pigment epithelial (RPE)-like cells invading the choroid, subretinal space and inner retina. This increase in MMP-2 mRNA expression peaked at day 10 whereafter a decline was detected. MMP-9 mRNA expression was low in untreated eyes and did not increase following laser treatment.
Conclusion:
The results show that MMP-2 mRNA expression is increased in experimental CNV, and support of a role for MMP-2 in the development of CNV in age-related macular degeneration.
Insights
Matrix metalloproteinase-2 (MMP-2) mRNA expression significantly increases in experimental choroidal neovascularization (CNV) in rats. This finding supports MMP-2
Area of Science:
- Ophthalmology
- Molecular Biology
- Biochemistry
Background:
- Matrix metalloproteinases (MMPs) are enzymes degrading extracellular matrix.
- MMP-2 and MMP-9 are implicated in ocular neovascularization.
- Choroidal neovascularization (CNV) is a key feature of age-related macular degeneration.
Purpose of the Study:
- To investigate the role of MMP-2 and MMP-9 in experimental CNV.
- To analyze the mRNA expression of MMP-2 and MMP-9 in a rat model of CNV.
Main Methods:
- CNV was induced in rats using krypton laser photocoagulation.
- Eyes were enucleated at various time points (1-60 days).
- In situ hybridization was used to analyze MMP-2 and MMP-9 mRNA expression.
Main Results:
- MMP-2 mRNA expression was low in untreated eyes but markedly increased in laser-treated eyes.
- Increased MMP-2 mRNA was localized to macrophage-like and RPE-like cells.
- MMP-2 mRNA expression peaked at day 10 post-laser treatment.
- MMP-9 mRNA expression remained low and did not increase after laser treatment.
Conclusions:
- MMP-2 mRNA expression is upregulated in experimental CNV.
- These findings support a role for MMP-2 in the pathogenesis of CNV.
- MMP-2 may be a therapeutic target for age-related macular degeneration.