Diurnal telemetry IOP in rabbits and monkeys: Effect of timolol

Abstract

Abstract: : Purpose: To evaluate diurnal IOP in awake un–restrained rabbits (normotensive) and monkeys (normotensive, glaucomatous) following surgical implantation of telemetry devices that continuously measure IOP, and to determine the IOP response to a standard ocular anti–hypertensive agent. Methods: Albino rabbits (2–4 kg) or cynomolgus monkeys (3–5 kg) were sedated with ketamine, intubated, and anesthetized with isoflurane. The scalp was prepared for aseptic surgery, followed by a 4 cm incision and tissue blunt–dissection to form a pocket in the underlying fascia to contain the pressure transducer (TA11PA–C40, DSI, Saint Paul, MN). The catheter from the tranducer was then guided subcutaneously to the orbit, and inserted into the vitreous cavity through a small opening in the pars plana which was sutured closed and fixed with tissue adhesive (OS–rabbits; OD–monkeys). Receivers were placed into the animal cages and connected to a computer running DSI’s dataquest software for data capture. Animals were housed in a 12 hours light, 12 hours dark cycle: 6:00 AM ON, 6:00 PM OFF. One group of monkeys underwent unilateral argon laser photocoagulation of the trabecular meshwork to produce ocular hypertension at least 2 months prior to implantation of the telemetry device. After a recovery and stabilization period of 2–4 weeks, timolol was topically applied to the instrumented eye of rabbits and glaucomatous monkeys. Results:IOP in rabbits were lower during the day than at night. The maximum rise in IOP following lights–out was 6 ± 1.3 mm Hg (n=6) which occurred 2 hours after lights–out.. Timolol (0.5%) administered qd for 3 days @ 5:30 pm each day blunted the rise in IOP during the dark phase of the diurnal cycle. In normotensive monkeys (n=7), IOPs were 1–2 mm Hg lower in the dark phase, than in the light phase. In glaucomatous monkeys (n=6), IOPs were lower in the dark phase than the light phase by a maximum of 8 ± 2.3 mm Hg and occurred 3 hours following lights–out. Timolol (0.5%) applied at 9:00 am in the morning lowered IOP 35% during the day only; there was no drug effect at night. Conclusions:Diurnal IOP measurements in unfettered, conscious animals are possible with the DSI telemetry system. During the dark phase of the diurnal cycle, IOP increases in rabbits and decreases in monkeys. The dark–phase reduction in IOP is more pronounced in glaucomatous monkeys than in normotensive monkeys. Anti–glaucoma medications lower IOP in this model.

Keywords: intraocular pressure • wound healing