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Reduced choroidal neovascular membrane formation in matrix metalloproteinase-2-deficient mice
Lennart Berglin1, Sylvia Sarman, Ingeborg van der Ploeg
1Department of Ophthalmology, Karolinska Institute, Stockholm, Sweden.
Purpose:
Findings in studies have suggested a role for matrix metalloproteinase (MMP)-2 in angiogenesis, including choroidal neovascularization (CNV). To investigate further, the current study was conducted to observe the formation of experimental CNV in MMP-2-deficient mice.
Methods:
CNV was induced in wild-type and MMP-2-deficient mice by krypton laser photocoagulation of the fundus. The time-course of expression of MMP-2 mRNA after laser treatment was determined by in situ hybridization with anti-sense and sense cRNA probes. MMP-2 protein distribution was determined by immunohistochemistry. Ten days after treatment, the extent of CNV was evaluated on hematoxylin-eosin stained serial sections. The maximum height of the CNV lesions was calculated by image analysis of digitized histologic images.
Results:
Expression of MMP-2 mRNA was detected in the CNV lesions at day 3 after laser treatment and peaked at day 5, after which it slowly declined. MMP-2 mRNA expression appeared to be highest at the margins of the membrane. Immunostaining for MMP-2 confirmed the presence of MMP-2 protein in the CNV lesions. The CNV lesions of MMP-2-deficient mice showed that relative thickness was reduced by 31% compared with wild-type mice (P = 0.006).
Conclusions:
The present study demonstrated that MMP-2 mRNA and protein are upregulated during experimental CNV in the mouse. The marked difference in thickness of the CNV membrane between wild-type and MMP-2-deficient mice shows that MMP-2 is involved in the formation of experimental CNV in the mouse. These results suggest that pharmacologic targeting of MMPs, including MMP-2, may reduce formation of CNV in conditions such as age-related macular degeneration.
Insights
Matrix metalloproteinase-2 (MMP-2) plays a key role in choroidal neovascularization (CNV). MMP-2 deficient mice showed a 31% reduction in CNV lesion thickness, indicating MMP-2
Area of Science:
- Ophthalmology
- Molecular Biology
- Genetics
Background:
- Matrix metalloproteinase-2 (MMP-2) is implicated in angiogenesis.
- Choroidal neovascularization (CNV) is a significant cause of vision loss.
Purpose of the Study:
- To investigate the role of MMP-2 in experimental CNV formation.
- To compare CNV development in MMP-2-deficient mice versus wild-type mice.
Main Methods:
- Experimental CNV was induced using krypton laser photocoagulation in mice.
- MMP-2 mRNA and protein expression were analyzed using in situ hybridization and immunohistochemistry.
- CNV lesion thickness was quantified via histological analysis.
Main Results:
- MMP-2 mRNA and protein were upregulated in CNV lesions.
- MMP-2 mRNA expression peaked at day 5 post-laser treatment.
- CNV lesions in MMP-2-deficient mice were 31% thinner than in wild-type mice.
Conclusions:
- MMP-2 is demonstrably involved in the formation of experimental CNV.
- Targeting MMP-2 may offer a therapeutic strategy for CNV, such as in age-related macular degeneration.