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D.-J. Oh, Y. H. Ooi, D. J. Rhee; Expression of Tissue Inhibitors of Metalloproteinases Following Latanoprost and Unoprostone. Invest. Ophthalmol. Vis. Sci. 2007;48(13):2062.
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To examine differential expression levels of the tissue inhibitors of metalloproteinases (TIMPs) following incubation with latanoprost and unoprostone in human trabecular meshwork (TM) endothelial and ciliary body smooth muscle (CBSM) cells.
Cultures of human TM and CBSM cells isolated from corneoscleral rims of 3 donors were grown to confluence. Following 1-day of incubation with serum free media, the cells were treated with latanoprost (30 and 300 ng/mL), unoprostone (145 and 1450 ng/mL), or vehicle control for 24 hours. Changes in TIMP protein levels were assessed using immunoblotting.
In CBSM and TM cells, TIMP-1 did not significantly change. In CBSM cells, TIMP-1 increased 5% and 6% at pharmacologic doses of latanoprost and unoprostone (30 and 145 ng/mL), respectively. In TM cells, TIMP-1 decreased 0% and 5% at pharmacologic dose with latanoprost and unoprostone.At pharmacologic doses, TIMP-2 increased 16% and 24% in TM cells following latanoprost and unoprostone without significant changes in CBSM cells following latanoprost or unoprostone.TIMP-3 increased 17% in CBSM cells and 12% in TM cells at 30 ng/mL of latanoprost. TIMP-3 increased 20% at 145 ng/mL of unoprostone in CBSM cells, but was not changed in TM cells.In CBSM cells, TIMP-4 increased 19% and 31% at pharmacologic doses of latanoprost and unoprostone, respectively. In TM cells, TIMP-4 increased 23% at 30 ng/mL of latanoprost and 28% at 145 ng/mL of unoprostone. TIMP-4 increased about 10% at 10x the pharmacologic doses with both latanoprost and unoprostone.
In TM cells, latanoprost and unoprostone increased TIMP levels to a similar level. In CBSMs, unoprostone increased TIMP levels to a greater degree than latanoprost. The net effect of these changes could indicate that unoprostone may have a greater inhibitory effect on matrix metalloproteinase-mediated extracellular matrix (ECM) turnover. This may be the mechanism to explain latanoprost’s greater clinical IOP lowering and further implicate ECM turnover as a regulatory control for outflow resistance.
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