Abstract:

To examine the cytotoxic effect of betaxolol, a widely used anti-glaucoma drug, on human corneal epithelial (HCEP) cells and its underlying mechanisms, in vitro cultured HCEP cells were treated with betaxolol at different doses. And the growth situation and morphology of the cells were monitored with an inverted light microscope, plasma membrane permeability of them was detected by acridine orange/ethidium bromide (AO/EB) double-fluorescent staining, DNA fragmentation and ultrastructure of them were investigated by DNA agarose gel electrophoresis and transmission electron microscopy (TEM), respectively. It was found that betaxolol at doses of 0.17500-2.80000g/L showed significant cytotoxicity to HCEP cells. The cytotoxicity increased with dose and time, and most of the cells shrunk and died 24h post treatment. Furthermore, 0.17500-2.80000g/L betaxolol elevated the plasma membrane permeability of HCEP cells, induced DNA fragmentation, chromatin condensation, and apoptotic body formation as well. In conclusion, betaxolol at doses ranging from 0.17500 to 2.80000g/L has significant cytotoxicity to HCEP cells in dose-and time-dependent manners, which is realized by inducing apoptosis in these cells, suggesting the inescapable sever cytotoxic side effect of betaxolol in eye clinic.

Key words: human corneal epithelial cells; betaxolol; apoptosis; DNA fragmentation; apoptotic body