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R.L. Bruhn, S.M. Conley, P.V. Morgan, W.D. Stamer; Selenium Effects on Metalloproteinase Activity in Trabecular Meshwork Cell Supernatants . Invest. Ophthalmol. Vis. Sci. 2003;44(13):1173.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: A current selenium-supplementation intervention trial (the Nutritional Prevention of Cancer), based here at the University of Arizona, has seen an increased incidence of glaucoma as shown by an elevated hazard ratio (HR = 1.31;95% Confidence Interval =0.74-2.34) in the selenium-supplemented group. Since selenium has been shown to directly inhibit matrix metalloproteinases (MMPs) and elevate tissue inhibitors of metalloproteinases (TIMPs) in various types of cultured cells, the purpose of this study was to determine the effect of selenium on matrix metalloproteinase turnover in human trabecular meshwork (HTM) cells; a site of pathology in glaucoma. Methods: HTM cell cultures were dosed with the selenium compound, methylseleninic acid (MeSA), to determine the effects of selenium on MMP activity and MMP and TIMP secretion in vitro. Cells were exposed to 100 nM or 1 µM MeSA for 24 hours in serum free medium. Supernatants were collected, concentrated, and analyzed by zymography or by western blotting using monoclonal antibodies to MMP-2, MMP-9, TIMP-1, and TIMP-2. Results: Secretion of TIMP-1 appeared to decrease with increasing concentrations of MeSA (n=11). Limited analyses of TIMP-2 showed either no net change in overall protein secretion, or a slight increase in protein secretion (n=2). MMP-9 was not detectable by zymography or western blotting. We observed consistent increases in the appearance of the active form of MMP-2 (n=2), while overall appearance of the inactive form remained unchanged (n=11). MMP-2 zymography results showed that treatment with MeSA did not change the gelatinase activity of MMP-2 (inactive form, n=7), however the gelatinase activity of the active form of MMP-2 consistently decreased after treatment (n=5). Conclusion: These results are consistent with previously published studies of selenium's action on MMP-2 in cultures of human umbilical vein endothelial cells. The action of MeSA on secreted MMPs and TIMPs from HTM cells suggests a possible mechanism for selenium-induced increases in intraocular pressure and thus a possible mode of action for selenium-induced glaucoma.
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