Abstract
Purpose: :
We sought to measure intraocular pressure (IOP), outflow facility (C), and episcleral venous pressure (Pe), and deduce uveoscleral outflow (Fu) and aqueous formation rate (Fin), in the mouse eye.
Methods: :
Adult male Balb/c mice were anesthetized. Resting IOP was determined (TonoLab). The anterior chamber was then cannulated (30G needle) and infused at constant flow rate (BSS-Plus®, 0.1-0.5µL/min, 0.1µL/min increments). Pressure developed was determined (pressure transducer). Clive was estimated from 1/(slope of regression line through Pressure-Flow Rate curve). Pe was estimated manometrically by lowering reservoir until Schlemm’s canal was observed to swell/redden (episcleral venous reflux). Animals were killed, eliminating Fin and Pe, and C determined again (Cdead). Fudead was deduced: Fudead = F-(IOPdead×Cdead), where F = perfusate flow rate. By assuming Fudead = Fulive, Fin was deduced: Fin = [(Clive×(IOP-Pe)]+Fudead.
Results: :
In 4 control mice, anesthetized IOP was 9.9±0.3mmHg (mean±SEM, n=8 eyes). Clive was 0.011±0.0005µL/min/mmHg. Cdead was unchanged (0.011±0.001 µL/min/mmHg, P=0.8). Pe was 4.9±0.4mmHg. Fin was 0.081±0.018µL/min. Fu was 0.034±0.014µL/min (32.0±9.7% of Fin). In 7 mice, right eyes (OD) received 10µL Xalatan® (latanoprost, 0.005%) at 25, 19, & 1h prior to cannulation. Left eyes (OS) received vehicle (Veh). Xalatan reduced IOP from 11.1±0.5mmHg (Veh) to 7.7±0.3mmHg (P<0.001, n=7 eyes). Clive increased from 0.011±0.002µL/min/mmHg (Veh) to 0.015±0.002 µL/min/mmHg (P=0.012), and Pe decreased from 5.0±0.3mmHg (Veh) to 3.7±0.4mmHg (P=0.049). Fin did not significantly change (0.101±0.014µL/min with Veh vs 0.092±0.012µL/min with Xalatan), and neither did Fu (0.038±0.018µL/min, 32.5±11.0% of Fin with Veh vs 0.032±0.013µL/min, 35.2±9.3% of Fin with Xalatan). In 8 further mice, OD received 10µL Betoptic-S® (betaxolol HCl, 0.25%) at 25, 19, & 1h prior to cannulation. OS received Veh. Betaxolol reduced IOP from 13.4±0.6mmHg (Veh) to 8.2±0.4mmHg (P<0.001, n=8 eyes). Fin decreased from 0.166±0.022µL/min (Veh) to 0.091±0.016µL/min (P=0.009). Clive (0.018±0.002µL/min/mmHg with Veh vs 0.018±0.001 µL/min/mmHg with betaxolol), Pe (4.6±0.3mmHg with Veh vs 4.2±0.2mmHg with betaxolol), and Fu (0.015±0.008µL/min (5.3±3.6% of Fin) with Veh vs 0.020±0.010µL/min (15.1±7.9% of Fin) with betaxolol) were not significantly changed.
Conclusions: :
Concurrent measurement of IOP, C, and Pe, and deduction of Fin and Fu, is feasible in the mouse eye. Xalatan lowers IOP by increasing C and reducing Pe. Betoptic-S lowers IOP by reducing Fin.Reference: Aihara, M., et al. IOVS 44: 5168-5173, 2003.
Keywords: aqueous • anterior chamber • inflow/ciliary body