Isopropyl unoprostone increases the activities of matrix metalloproteinases in cultured monkey ciliary muscle cells.
OBJECTIVE
The mechanism by which the prostaglandin F2alpha-related antiglaucoma compound isopropyl unoprostone (referred to as unoprostone) reduces intraocular pressure is largely unknown. Another prostaglandin F2alpha-related compound, latanoprost, influences the activities of matrix metalloproteinases in ciliary muscle. Unoprostone ophthalmic solution is metabolized to oxidized metabolites, mainly M1 and M2, in the eye. The aim of this study was to investigate whether intraocular metabolites of unoprostone, M1 and M2, change the metalloproteinase activity in cultured monkey ciliary muscle cells.


METHODS
Monkey ciliary muscle cells and trabecular meshwork cells were grown separately to confluence in monolayer cell cultures. M1 (10 nM, 100 nM, or 1 microM), M2 (10 nM, 100 nM, or 1 microM), 100 nM prostaglandin F2alpha, or vehicle solutions were added to each culture medium for 48 hours. The media were then assayed to measure metalloproteinase activities quantitatively by means of substrate zymography.


RESULTS
Compared with the vehicle controls, M1, M2, and prostaglandin F2alpha significantly increased the metalloproteinase-2 activity in cultured ciliary muscle cells in a dose-dependent manner, but did not affect the metalloproteinase-2 activity in cultured trabecular meshwork cells. All experimented prostaglandins slightly increased metalloproteinase-9 activity in ciliary muscle cells, although these changes were not significant.


CONCLUSIONS
The current results show that unoprostone influences the metabolism of the extracellular matrix in the ciliary muscle and that remodeling of the extracellular matrix in the ciliary muscle may be a possible mechanism by which unoprostone ophthalmic solution reduces intraocular pressure.
Kashiwagi
K
K
Department of Ophthalmology, Yamanashi Medical University, Tamaho, Japan. kenjik@res.yamanashi-med.ac.jp
Jin
M
M
Suzuki
M
M
Tanaka
Y
Y
Iizuka
Y
Y
Tsukahara
S
S
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D002924:Ciliary Body / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D015237:Dinoprost / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D008252:Macaca fascicularis; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D014129:Trabecular Meshwork / Q000166:cytology / Q000187:drug effects / Q000201:enzymology
D000959:Antihypertensive Agents; C072630:isopropyl unoprostone; D015237:Dinoprost; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9