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B. Govindarajan, R. G. Salomon, S. K. Bhattacharya, B. Anand-Apte; Role of Oxidatively Modified Extracellular Matrix Proteins and Matrix Metalloproteinases in Glaucomatous Trabecular Meshwork. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1645.
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© ARVO (1962-2015); The Authors (2016-present)
To compare the levels of matrix metalloproteinase’s (MMP’s) in normal and glaucomatous human and mouse trabecular meshwork (TM). To determine the differences in levels of fibronectin expression in the normal and glaucomatous TM. To determine the effect of modification of fibronectin in vitro by 4-hydroxynonenal (HNE) and to determine the effect of MMP-2 on modified fibronectin.
Gelatin zymography and ELISAs were used to analyze MMP activity in control and glaucomatous TM tissue. Western blot analysis was performed using rabbit polyclonal antibodies to MMP’s and fibronectin. Plug filled gel electrophoresis (PFGE) was utilized to capture the aggregates of fibronectin. Human fibronectin was modified in vitro by HNE and subjected to western blot analysis using fibronectin antibodies and polyclonal antibodies against HNE. The effect of MMP-2 on the degradation of modified fibronectin was examined.
MMP-2 and 9 levels were lower in the glaucomatous TM than in the normal. Western blot analysis identified aggregated as well as degraded forms of fibronectin in normal TM. PFGE analysis identified fibronectin aggregates in the normal TM as opposed to the glaucomatous TM. Pro-MMP-2 can be activated in vitro by the addition of HNE and is incapable of degrading fibronectin modified by HNE at high concentrations.
Reduced expression of MMPs in glaucomatous TM as well as oxidatively modified extracellular matrix proteins may play a role in the modulation of ECM turnover and the pathogenesis of glaucoma.
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