Continuous intraocular pressure measurement by telemetry in alpha-chymotrypsin-induced glaucoma model in the rabbit: effects of timolol, dorzolamide, and epinephrine.
The aim of this study was to set-up and validate the use of a radio-telemetry system in order to record IOP in chronic ocular hypertensive animals. The transmitter of a miniaturized radio-telemetry system was implanted in rabbits, and its catheter was tunnelled subcutaneously to the superior conjunctival sac and inserted into the midvitreous. Implantation was performed in chronic ocular hypertensive rabbits induced by an injection of alpha-chymotrypsin into the posterior chamber of the eye. The effects of 0.5% timolol maleate, 2% dorzolamide hydrochloride and 1% epinephrine were assessed and compared after topical administration in this model. Implanted radio-telemetric system into the vitreous allowed IOP measurement for more than 6 months. In this study, circadian IOP kinetic profiles were monitored in all animals over 24 h for 3 weeks. Timolol maleate was found significantly potent in reducing IOP, while changes depended on the nyctemeral period. Dorzolamide hydrochloride induced a very large IOP reduction and was found to be also well effective at night. We evidenced a biphasic time-dependent effect after topical epinephrine, with a long lasting IOP increase occurring after the administration. This change was found to be related to side effects resulting from a poor ocular tolerance of this drug in the rabbit, leading to either a complete eye closure or a higher blinking rate. By using our method, we confirmed the pressure pulses and undershoots occurring during blinking. Radio-telemetry in chronic glaucoma rabbits appears as a refined method to assess anti-glaucoma drug activity, 24 hours a day, for long-term periods in unrestrained animals, while also providing information on the ocular side effects of eye drops.
Percicot
C L
CL
Ciba-Vision Ophthalmics, International Ophtha R&D, Basle, Switzerland.
Schnell
C R
CR
Debon
C
C
Hariton
C
C
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D002918:Chymotrypsin; D002940:Circadian Rhythm; D004195:Disease Models, Animal; D004837:Epinephrine / Q000494:pharmacology*; D005260:Female; D005901:Glaucoma / Q000139:chemically induced / Q000188:drug therapy*; D007429:Intraocular Pressure / Q000187:drug effects*; D009883:Ophthalmic Solutions; D011817:Rabbits; D013449:Sulfonamides / Q000494:pharmacology*; D013686:Telemetry; D013876:Thiophenes / Q000494:pharmacology*; D013999:Timolol / Q000494:pharmacology*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002257:Carbonic Anhydrase Inhibitors; D009883:Ophthalmic Solutions; D013449:Sulfonamides; D013876:Thiophenes; D013999:Timolol; C062765:dorzolamide; D002918:Chymotrypsin; D004837:Epinephrine