Cell Injury Effect of Isopropyl Unoprostone, an Antiglaucoma Agent, on Cultured Human Conjunctival Cells

Abstract

Corneal epithelial disorders due to isopropyl unoprostone (unoprostone) eye drops, a prostaglandin F2alpha-related substance and antiglaucoma agent, have been reported since the agent became commercially available. The in vitro study was performed to clarify the mechanism of cell injury due to unoprostone. After Chang's human conjunctival cells were cultured and exposed for 2, 4 and 8 min to 0.03, 0.06, and 0.12% unoprostone and its vehicle containing 1% polysorbate 80, a cell growth assay and DNA histogram analysis using a flow cytometer and scanning electron microscopy were performed. The number of living cells was reduced, and the floating cell number increased immediately after exposure to 0.12% unoprostone for 8 min. When the cells were cultured for another 48 hr after exposure to unoprostone, the cell number was reduced dose and time dependently. Exposure for 2 min to 0.12% unoprostone showed no effect on the cell cycle. However, exposure for 2 min to 0.12% unoprostone caused alteration of the cell surface, such as reduction of microvilli and filopodia. The vehicle did not affect the cell surface or cell growth. These results suggest that clinically instilled eye drops ofunoprostone can affect cell structure, inhibit cell growth, and gradually cause corneal epithelial disorders.

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“…It is interesting to note that the effect of unoprostone is better than that of latanoprost, whether tested in vitro or in vivo . Similar studies have revealed that unoprostone has a more inhibitory effect on cellular proliferation than latanoprost in cultured conjunctival cells [26]. However, it may be explained that latanoprost displays a strong ability to decrease conjunctival collagen density [13], and it also causes the expression of transforming growth factor‐β, which may stimulate cellular proliferation [27].…”