Measurement of IOP and drug administration

In all the animal studies, male, ocular normotensive, cynomolgus monkeys were used. Prior to the study, all the monkeys have undergone training to be restrained in a monkey chair (CL-4535; Primate Products, Miami, FL, USA) and also to go through IOP measurements without the use of sedation or general anaesthesia. In order to measure IOP, each monkey was restrained in the monkey chair, in sitting position, and the topical application of the local corneal anaesthesia was made with 0.4% oxybuprocaine solution (Benoxil ophthalmic solution 0.4%; Santen Pharmaceutical Co., Ltd., Osaka, Japan) to the monkey’s eyes. Then, IOP was measured using a pneumatonometer (Model 30 Classic; Reichert Technologies, Depew, NY, USA). In all the studies, the right eye of each monkey was administered either saline or test drugs between 9:30 AM and 11:00 AM, with the contralateral eye kept untreated.