Reliable measurement of mouse intraocular pressure by a servo-null micropipette system

PURPOSE. TO develop a reliable technique for measuring intraocular pressure (IOP) in the mouse. METHODS. An electrophysiologic approach-the servo-null micropipette system (SNMS)-for measuring hydrostatic pressure was adapted for the mouse eye. Fi ne-tipped (5 mum in diameter) micropipettes were advanced across the cornea with a piezoelectric micromanipulator, and the IOP was continuously monito red for up to 46 minutes. RESULTS. The micropipette tip was visualized in the anterior chamber. With the SNMS, the IOP of black Swiss outbred mice under ketamine anesthesia was 17.8 +/- 0.4 mm Hg, higher than values previously estimated in inbred mous e strains by a larger bore microneedle manometric technique. After withdraw al of the micropipette, a second penetration led to a similar level of IOP. Hypotonic solutions increased and hypertonic solutions decreased IOP. Drug s that decrease inflow (acetazolamide, timolol) or increase outflow facilit y (pilocarpine, latanoprost) in primates and humans lowered steady state IO P in the mouse. The transient initial increase in IOP produced by pilocarpi ne reported in other animals was also observed in the mouse. Xylazine-ketam ine anesthesia lowered IOP substantially in comparison with systemic anesth esia with either ketamine or tribromoethanol alone. CONCLUSIONS. The SNMS is the first reliable, reproducible method for measur ing mouse IOP. The mouse IOP is sensitive not only to drugs known to reduce aqueous humor inflow but also to drugs that increase aqueous humor outflow facility in the eyes of primates and humans. The development of the SNMS i s an enabling step in the use of the mouse for glaucoma research, including molecular genetics, molecular pharmacology, and the search for novel antig laucoma drugs.