Unoprostone isopropyl pretreatment decreases endothelin-1 release and the intra-ocular pressure spike induced by laser trabeculoplasty in the rabbit

Abstract

Purpose: We have previously shown that the intra-ocular pressure (IOP) spike due to argon laser trabeculoplasty (ALT) is caused by an acute endothelin-1 (ET-1) release from the uveal tissue into the aqueous humour of rabbit eyes. In this study we investigated whether pretreatment with topical unoprostone isopropyl, a functional antagonist of ET-1, protects against the pressure spike due to ALT in the rabbit model.

Methods: IOP of both eyes of 17 pigmented rabbits was measured with a TonoPen XL tonometer under general anaesthesia (baseline measurement). Then the right eyes were treated with topical unoprostone isopropyl 0.12% BID for 6 days, and the left eyes similarly received balanced salt solution (BSS) twice daily. After the last morning instillation, IOP for both eyes was measured under general anaesthesia after 2 h in group 1 and after 3 h in group 2 animals. Then, for both groups, ALT was performed on both eyes. Thirty minutes after laser treatment (and still under general anaesthesia), IOP was measured again. Then the aqueous humour was aspirated for measurement of ET-1 concentration.

Results: Baseline individual IOP differences (left eye minus right eye) were not significant in both groups: mean +/- SD 0.25 +/- 1.16 and -0.33 +/- 0.71 mm Hg, respectively (paired t test, p > 0.05 for both groups). On day 6, 2 h (group 1) and 3 h (group 2) after the last instillation but before laser trabeculoplasty, the difference (BSS-pretreated left eye minus unoprostone-pretreated right eye) increased to 2.13 +/- 2.10 mm Hg (p = 0.024) and 1.33 +/- 0.71 mm Hg (p = 0.0005), respectively. Thirty minutes after ALT, the IOP difference was 2.63 +/- 2.67 mm Hg in group 1 (p = 0.027), but no difference was seen in group 2 (0.67 +/- 1.94 mm Hg, p = 0.332). In group 1, postoperative aqueous humour ET-1 concentration for the unoprostone-pretreated right eye was significantly lower than that for the BSS-pretreated left eye (paired t test, p = 0.01); but in group 2 no inter-ocular difference in ET-1 concentration was found (p = 0.976).

Conclusion: Topical unoprostone pretreatment decreases laser-induced ET-1 release and diminishes the IOP spike caused by ALT in vivo within 2 h after instillation, when the concentration of unoprostone in the aqueous humour is high.