Topical application of AMA0076, a locally acting rho kinase (ROCK) inhibitor, results in a robust IOP control in Dutch Belted Rabbits

Abstract

AbstractPurpose To determine the intra ocular pressure (IOP) lowering efficacy of the local ROCK inhibitor, AMA0076, in Dutch Belted rabbits.Methods Dutch Belted rabbits (5 rabbits/group) received topically a single dose of AMA0076 in one eye. A concentration range of 0.031 ‐ 0.625% AMA0076 was tested. The contralateral eye served as control and was treated with saline. IOP was measured at baseline and 30 min, 1, 2, 3, 4, 5, 6, 7, 8h post topical administration.Results Single topical administration of AMA0076 significantly lowered IOP in all groups compared to the control eye (p<0.05). Mean baseline IOP during the experiments was between 20.6 and 21.5 mmHg. Thirty minutes after topical treatment, a concentration dependent reduction in IOP was demonstrated with a ΔIOP ranging from 3.9mmHg – 7mmHg compared to the control eye. Maximal IOP reduction of each concentration following single dose administration of AMA0076 was observed ±2 hours after instillation with a ΔIOP ranging from 4.6mmHg and 7.5mmHg. The IOP lowering effect with the highest concentrations of AMA0076 (0.625% and 0.125%) was sustained during the experiment.Conclusion AMA0076 was effective in rapidly lowering IOP in a dose depended and sustained manner after a single topical dose in Dutch Belted rabbits. This new class of local ROCK inhibitors has potential therapeutic value for the IOP lowering treatment of glaucoma.