The effects of timolol on the active transport across the ciliary epithelium.

The mean transepithelial potential was +4.04 mV (cameral side positive to stroma). The results (Fig. 1) show that the short-circuit current was significantly reduced by timolol at 10(-4) and 10(-2) M (p less than 0.01). Since the short-circuit current across the isolated ciliary epithelium is a measure of active sodium transport in the direction stroma----posterior chamber there is an appreciable fall in Na +/- transport across the ciliary epithelium at a timolol concentration of 10(-4) M. On current values of aqueous humour secretion there would be a corresponding fall in aqueous production. For comparison it is worth recalling that the concentration of timolol in 0.5 per cent eye drops is slightly over 10(-2) M. Exposure of the tissue to timolol, a beta blocker does not seem to affect the subsequent response of the system to isoprenaline, a beta stimulant. A significant stimulation of short circuit current in the dose-range of 10(-4) to 10(-3) M with isoprenaline in a similar preparation was reported by Cole and Nagasubramanian and increase of short-circuit current and/or sodium transport in amphibian epithelia have been reported for catecholamines, and this effect may possibly be due to a decrease of the resistance to ions actively transported by the 'sodium pump' mechanism brought about via cyclic-AMP mediating the action at a cellular level. It appears that timolol has a direct effect on the active transport per se and by reducing the active ion influx can cause a reduction in the volume of aqueous production.