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To evaluate the protective effects of the matrix metalloproteinase (MMP) inhibitor GM6001 against simvastatin-induced damage to the trabecular meshwork (TM). TM cells were treated with simvastatin (10 µmol/L) and GM6001 (2.5, 5, and 10 µmol/L) for 24 hours. MMP-1, MMP-2, and MMP-9 activities were determined using gelatin zymography. Protein levels of MMP-1, MMP-2, MMP-9, and tissue inhibitor of metalloproteinase 1 (TIMP-1) were analyzed by Western blotting. Effects of simvastatin and GM6001 on TM cell apoptosis were assessed by flow cytometry. Treatment of TM cells with simvastatin increased MMP-9 activity and expression of MMP-1 and MMP-2. This effect was reduced in a dose-dependent manner by co-treatment with GM6001. Similarly, the level of TIMP-1 was decreased following treatment with simvastatin and markedly increased in GM6001-treated groups. Simvastatin induced TM cell apoptosis, and this effect was inhibited by GM6001. Simvastatin causes disruption of the TM by reducing TM cell survival through MMP-1 and MMP-2 upregulation. Co-treatment with the MMP inhibitor GM6001 improved TM cells resistance to the detrimental effect of simvastatin, through the inhibition of MMP-9 activity, MMP-1 and MMP
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