The bovine perfused eye as a model for pharmacological investigations

The isolated perfused eye of many species has become a frequently used model in the study of ocular pharmacology. Due to its availability, cheapness and comfortable size for experimental use the bovine eye provides an attractive model for conducting perfusion experiments. Although initially rejected by Kishida et al. (1985), the bovine perfused eye has been proved to be a valid model for studying aqueous humour dynamics and the pharmacology of various antiglaucoma drugs, including the β-adrenoceptor antagonist, timolol, and the carbonic anhydrase inhibitor, MK-927 (Wilson et al., 1993). A general aim of this study was to develop the in vitro bovine perfused eye, to show whether it is a useful model for experimental work in studying drug mechanisms in the eye, whether from a pharmacodynamic or pharmacokinetic point of view. Pharmacodynamic Study The procedure for dissection and setting up of the constant flow method for the bovine perfused eye was initially described by Wilson and co-workers (1993). Bovine eyes, obtained from the local abattoir, were cannulated via the long posterior ciliary artery and perfused with Krebs' solution. In order to monitor drug effects on intraocular pressure the anterior chamber was cannulated and connected to a water manometer. Since some drugs affect vascular resistance, the arterial perfusion pressure was continuously measured. Drug solutions or vehicles were administered by one of three routes; (i) by addition of drug to the perfusate reservoir at an exact concentration, (ii) as a bolus dose injected intra-arterially or (iii) as a bolus dose injected intracamerally. Constriction of the pupil, in response to pilocarpine (10 -6M), shown by a significant decrease in pupil diameter, indicated that following intra-arterial administration, drugs have access to the anterior segment of the eye, including the iris sphincter and therefore very probably the ciliary muscle, since their arterial supply is common. To investigate the bovine perfused eye as a model for studying intraocular pressure and aqueous humour dynamics, we studied four different drugs known to alter either aqueous humour formation or aqueous humour outflow. The results show that experimentally damaging the cornea, effectively removing the barrier properties of the corneal epithelium, increases the amount of aciclovir absorption in the cornea and aqueous humour compared with the undamaged cornea. The observed increases in absorption of aciclovir following experimental damage are much greater when the drug formulations have hydrophilic properties, such as the PVA film and aqueous gel. From the present work, the formulations can be ranked in order of corneal and aqueous humour absorption of aciclovir: Ointment < PVA Film < Aqueous Gel In this model the level of drug penetration in the cornea and aqueous humour can be measured without the complications associated with in vivo studies. Due to the lack of in vivo factors such as blinking, drug dilution, drainage and conjunctival absorption the levels of absorption found in the present model are likely to be exaggerated. Nevertheless, the bovine perfused eye provides a useful model for pharmacokinetic studies, which is perhaps superior to the isolated corneal preparation nominally used to assess corneal drug absorption since conditions are more physiological and no edge-damage has been inflicted on the cornea