Reduced choroidal neovascular membrane formation in matrix metalloproteinase-2-deficient mice.
OBJECTIVE
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.
Berglin
Lennart
L
Department of Ophthalmology, Karolinska Institute, Stockholm, Sweden.
Sarman
Sylvia
S
van der Ploeg
Ingeborg
I
Steen
Björn
B
Ming
Yue
Y
Itohara
Shigeyoshi
S
Seregard
Stefan
S
Kvanta
Anders
A
D000818:Animals; D020256:Choroidal Neovascularization / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D004195:Disease Models, Animal; D005260:Female; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D017075:Laser Coagulation; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D015347:RNA Probes; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation
D015347:RNA Probes; D012333:RNA, Messenger; D020778:Matrix Metalloproteinase 2