Dhk. Ma et al., Expression of matrix metalloproteinases 2 and 9 and tissue inhibitors of metalloproteinase 1 and 2 in inflammation-induced corneal neovascularization, OPHTHAL RES, 33(6), 2001, pp. 353-362
Purpose: Matrix metalloproteinases (MMPs) and tissue inhibitors of metallop
roteinase (TIMPs) have been linked to the angiogenic process in general. In
order to understand the potential roles of MMP-2, MMP-9 and TIMPs in the c
orneal neovascularization process, we examined the expression and activitie
s of MMP-2, MMP-9 and TIMPs during the course of cauterization-induced corn
eal neovascularization in a rat model. Methods: Neovascularization of rat c
orneas was induced by silver nitrate cauterization. The expression of MMP-2
, MMP-9, TIMP-1 and TIMP-2 was examined by immunohistochemistry and RT-PCR.
The protein activities of MMPs and TIMPs were compared in pre- and postcau
terization corneas by gelatin zymography and reverse zymography, respective
ly. Results: MMP-2, TIMP-1 and TIMP-2 immunoreactivities were expressed in
normal corneas, predominantly in the corneal epithelium. After injury, immu
noreactivities of both MMPs and TIMPs were increased, notably in the healin
g corneal epithelium, infiltrating inflammatory cells, stromal fibroblasts
and ingrowing vascular endothelial cells. The increase in gross MMP-2 enzym
atic activity paralleled the maximal vascular ingrowth on day 4, while the
gross MMP-9 enzymatic activity rose immediately on day 1, then decreased st
eadily, which paralleled the magnitude of inflammatory cell infiltration. T
he immunoreactivity of MMPs/TIMPs decreased significantly 2 weeks after cau
terization. On day 35, MMP-2, TIMP-1 and TIMP-2 staining was seen only in c
orneal epithelium and vascular endothelial cells. Both the RT-PCR and rever
se zymography results revealed a more constant expression of TIMP-2, while
the TIMP-1 expression appeared to be more inducible. Conclusion: MMPs as we
ll as TIMPs were upregulated in cauterization-induced corneal neovasculariz
ation, suggesting that both may participate in extracellular matrix remodel
ing in the corneal wound healing, inflammation and neovascularization proce
sses. Copyright (C) 2001 S. Karger AG, Basel.