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J. C. Millar, I.-H. Pang, A. F. Clark; Aqueous Humor Dynamics in the Mouse by Constant Flow Infusion. Invest. Ophthalmol. Vis. Sci. 2008;49(13):354.
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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.
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.
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.
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.
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