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D.-J. Oh, Y. H. Ooi, D. J. Rhee; Relative Changes in Matrix Metalloproteinases and Tissue Inhibitors of Metalloproteinases Following Latanoprost, Bimatoprost, and Unoprostone in Human Ciliary Body Smooth Muscle Cells. Invest. Ophthalmol. Vis. Sci. 2008;49(13):1606.
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© ARVO (1962-2015); The Authors (2016-present)
To examine differential expression levels of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) following incubation with latanoprost, bimatoprost, and unoprostone in ciliary body smooth muscle (CBSM) cells.
Cultures of human CBSM cells isolated from corneoscleral rims of 13 donors were grown to confluence. Following 1 day of incubation with serum free media, the cells were treated with vehicle control (0.03% ethanol), latanoprost (0.03 µg/ml), bimatoprost (0.01 µg/ml), or unoprostone (0.145 µg/ml) for 24 hours. Changes in MMPs’ protein and enzymatic activity levels were assessed. Western blotting was used to assess relative changes in protein levels. Zymography was used to assess relative changes in enzyme activity of MMPs-1, -2, -3, and -9. Cell lines from five donors were used to determine the relative effects for each of the MMPs and TIMPs. Repeated immunoblots were performed revealing a variability of approximately 10% in our measurements. GAPDH served as an endogenous control. Results are presented as the mean ± SEM.
Latanoprost, bimatoprost, and unoprostone all increased pro-MMPs-1,-3, and -9 an average of 23% ± 5%, 54% ± 12%, and 86% ± 35%, respectively. Pro-MMP-2 and MMP-24 remained within 10% of control with all medications.On zymography, latanoprost increased the activity of MMP-9 an average of 19% ± 4%; bimatoprost and unoprostone did not significantly alter the activity of MMP-9. Similar to previous findings, only the intermediate form of MMP-1 was identified, but it did not show a significant change in enzyme activity. The active form of MMP-3 was not identified on zymography, as was also shown in previous reports.Latanoprost decreased TIMP-1 by 35% ± 16% while bimatoprost had no significant effect, and unoprostone increased TIMP-1 by 100% ± 20%. Latanoprost and bimatoprost did not affect the level of TIMPs-2 and -4 whereas unoprostone increased TIMP-4 by 85% ± 22%. Latanoprost, bimatoprost, and unoprostone increased TIMP-3 by 70% ± 15%, 57% ± 23%, and 57% ± 9%, respectively.
Latanoprost, bimatoprost, and unoprostone all increased MMPs-1, -3, and -9 with comparable effects. Unoprostone increased TIMPs compared to latanoprost and bimatoprost. Our findings support the hypothesis that the MMP:TIMP ratio correlates to IOP regulation and may explain the lower clinical efficacy of unoprostone in lowering IOP.
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