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Abstract #27630 Published in IGR 12-4
Novel methodology to record pharmacologically induced changes in intraocular pressure in conscious freely moving rats
Edye M; West H; Wickens J; Nguyen CpA2 Online 2009; 7:4
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(registered trademark). In agreement with clinical and experimental literature, we recorded a significant decrease in IOP of 4.1(plus or minus) 0.6mmHg (mean difference(plus or minus) 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(plus or minus) 0.29mmHg, mean difference(plus or minus) 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.
M. Edye. Pfizer Ltd., SandwichUnited Kingdom.
Classification:
5.1 Rodent (Part of: 5 Experimental glaucoma; animal models)
