Novel methodology to record pharmacologically induced changes in intraocular pressure in conscious freely moving rats

Michelle Edye, Heather West, Jeremy Wickens, Christine Nguyen. Pfizer Ltd. Sandwich, United Kingdom.

The measurement of intraocular pressure (IOP) is well established both clinically and pre-clinically to investigate glaucoma and its pharmacological treatment. IOP is homeostatically regulated through a balance between inflow and outflow of the aqueous humour within the eye. A number of different receptors are present on structures involved in regulating aqueous humour production and drainage, and thus IOP could potentially be a translatable biomarker for a number of drug development targets.

An anaesthetised rat IOP model was initially established using the clinically developed tonopen®. In agreement with clinical and experimental literature, we recorded a significant decrease in IOP of 4.1± 0.6mmHg (mean difference± SEM) following an i.v. bolus of the pressure lowering standard 20% mannitol (1.5g/kg) compared to vehicle (p<0.05; n = 3-4). To overcome the time restraints evident in anaesthetised models and to follow longer term changes in a higher throughput model, we have developed a telemetry model to record IOP in freely moving conscious rats in their home environment.

A radiotelemetric pressure transducer (DSI PhysioTel PA-C10, Data Sciences Int., St. Paul Minn., USA) was surgically implanted into the dorsal neck muscles of Sprague-Dawley rats and the catheter tunnelled subcutaneously with the tip positioned in the vitreous chamber of the rat’s eye (adapted from Valderrama et al., 20081). IOP was then recorded remotely in conscious freely moving rats for the duration of probe life. Following recovery from surgery, a 24 h diurnal variation in IOP (1.55± 0.29mmHg, mean difference± SEM; p<0.05; n = 6) was observed, as expected. Preliminary data with mannitol in this conscious telemetry model shows a trend to decrease IOP in concordance with earlier anaesthetised studies.

In summary, a novel methodology to record pharmacologically induced changes in IOP in conscious freely moving rats is presented here, with the potential to be a translatable biomarker.

1Valderrama et al. 2008 Direct effect of light on 24-h variation of aqueous humor protein concentration in Sprague–Dawley rats. Exp Eye Res. 2008 Nov;87(5):487-91.