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Rie Miyamoto, Naoya Miyamoto, Shingo Ishibashi, Hiroyuki Kondo, Akihiko Tawara; Timolol Activates MMP9 Via Membrane-anchored Protease Regulator Reck In Human Trabecular Meshwork Cells. Invest. Ophthalmol. Vis. Sci. 2012;53(14):3231.
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The major structural change in the human trabecular meshwork (TM) of eyes with primary open-angle glaucoma (POAG) is an increase in extracellular matrix (ECM) in the juxtacanalicular region of the TM. RECK, a glycosylphosphatidylinositol-anchored glycoprotein, inhibits the enzymatic activities of matrix metalloproteinases (MMPs), MMP2 and 9. Previous study has shown that RECK negatively regulated MMP9 transcription level. In this study, we investigate whether RECK affects factors responsible for the activity of MMPs in human TM cell cultures and a novel effect of anti-glaucoma agents .
The expression and activity of the MMPs and RECK was investigated using immortalized TM cell lines, NTM5 cells and GTM3 cells, which were derived from normal and glaucomatous TM, respectively, by western blot analysis, invasion assay and zymography. Cells were treated with anti-glaucoma drugs then analyzed for the expression of MMP2, and 9, and RECK using western blot analysis and zymography.
Both the expression and activity of MMP9 were high in glaucomatous TM cells when compared with normal TM cells. On the other hand, RECK expression was lower in glaucomatous than normal TM cells. There was no difference in expression and activity of MMP2 between glaucomatous and normal TM cell lines. In invasion assay, we also observed that glaucomatous TM cells invaded matrigel more than nomal TM cells. Furthermore, timolol induced the expression of MMP9, in contrast, reduced RECK expression. On the other hand, the expression of both MMP9 and RECK was no defference with treating tafluprost.
These results show for the first time that timolol possesses a novel effect that activates MMP9 via RECK inactivation transcriptional level in TM cells.
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