Abstract
Purpose :
The eyes of lab animals are similar structurally and functionally and are often applied equally as tools for studying the efficacy and toxicology of innovative drugs. In this study we report a discovery that clinically healthy dog and monkey had different responses to two glaucoma drugs (timolol and latanoprost). This case demonstrated that animal selection is sometimes critical in preclinical tests of ocular drugs.
Methods :
For dog experiments, 12 male beagle dogs (aged 9.1~18.1m; 13.0m in average) were dosed with 2 drops of 0.5% timolol eye drops (100 ul) twice a day in the right eyes for 7 days, and the contralateral eyes were dosed with saline as controls. IOP of both eyes was measured before next dosing in conscious animals. After the 7-day dosing and a 7-day washout period, the dogs were dosed with 2 drops of 0.005% latanoprost eye drops (100 ul) in the right eyes twice daily for 14 days, and the contralateral eyes were dosed with saline. IOP of both eyes was followed with same procedure. For monkey experiment, 6 male cynomolgus monkeys (aged 14.9~20.5y; 17.7y in average) were divided into 2 groups, 3 of them were dosed with 1drop of 0.5% timolol eye drops (50 ul) in both eyes once a day for 5 days, 3 of them were dosed with 50ul saline both eyes as the control. IOP was measured before each dosing. All of the IOP measurements were performed without anesthesia.
Results :
(1). Dog timolol group had similar IOP level to that of saline controls during 7 days dosing period suggesting timolol had no effect on the dogs. (2). Dog latanoprost group had lower IOP during dosing period and the reduction effect was observed after the first dose. (3). Monkey timolol group had significant lower IOP after the first dose and became stable after 2 doses. The reduction of IOP was about 30% of pre-dose values.
Conclusions :
IOP of dog and monkey responded differently to timolol and latanoprost treatment. The IOP of healthy dog was reduced by latanoprost but not by timolol in twice daily dosing regimen, while the IOP of healthy monkey was reduced by timolol in once daily dosing regimen. This case of different IOP responses demonstrated the importance of animal species in efficacy test of ocular drugs.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.