Isopropyl unoprostone increases the activities of matrix metalloproteinases in cultured monkey ciliary muscle cells

Purpose: The mechanism by which the prostaglandin F-2 alpha-related antigla ucoma compound isopropyl unoprostone (refer-red to as unoprostone) reduces intraocular pressure is largely unknown. Another prostaglandin F-2 alpha-re lated compound, latanoprost. influences the activities of matrix metallopro teinases in ciliary muscle. Unoprostone ophthalmic solution is metabolized to oxidized metabolites, mainly M1 and M2, in the eye. The aim of this stud y was to investigate whether intraocular metabolites of unoprostone, M1 and M2, change the metalloproteinase activity in cultured monkey ciliary muscl e cells. Materials and Methods: Monkey ciliary muscle cells and trabecular meshwork cells were grown separately to confluence in monolayer cell cultures. M1 (1 0 nM, 100 nM, or 1 muM), M2 (10 nM, 100 nM, or 1 muM) 100 nM prostaglandin F-2 alpha, or vehicle solutions were added to each culture medium for 48 ho urs. The media were then assayed to measure metalloproteinase activities qu antitatively by means of substrate zymography. Results: Compared with the vehicle controls, M1, M2. and prostaglandin F-2 alpha Significantly increased the metalloproteinase-2 activity in cultured ciliary muscle cells in a dose-dependent manner, but did not affect the met alloproteinase-2 activity in cultured trabecular meshwork cells. All experi mented prostaglandins slightly increased metalloproteinase-9 activity in ci liary muscle cells, although these changes were not significant. Conclusions: The current results show that unoprostone influences the metab olism of the extracellular matrix in the ciliary muscle and that remodeling of the extracellular matrix in the ciliary muscle may be a possible mechan ism by which unoprostone ophthalmic solution reduces intraocular pressure.