Assessment of aqueous humor dynamics in the mouse by a novel method of constant-flow infusion.
OBJECTIVE
To characterize a technique that concurrently assesses all aqueous humor hydrodynamic parameters in mouse eyes.


METHODS
Mouse outflow facility (C) was determined by multiple flow-rate infusion and episcleral venous pressure (Pe) measured by manometry. The animals were then euthanatized, eliminating aqueous formation rate (Fin) and Pe. C was determined again (C(dead)) while uveoscleral outflow (Fu(dead)) and Fin were deduced. To assess whether Fu(dead) would remain the same as Fu(live), the animals were perfused with FITC-dextran and Fu determined. The effects of IOP-lowering drugs on the parameters of aqueous hydrodynamics were also evaluated.


RESULTS
Under the conditions tested, Fu(live) (0.012 ± 0.003 μL/min) was not different from Fu(dead) (0.015 ± 0.003 μL/min; P = 0.472). In anesthetized mice, IOP = 11.4 ± 0.2 mm Hg (mean ± SEM, n = 8), C = 0.018 ± 0.0006 μL/min/mm Hg, Pe = 5.4 ± 0.2 mm Hg, Fin = 0.14 ± 0.0007 μL/min, and Fu = 0.029 ± 0.005 μL/min. C(dead) was not different from C (P = 0.317). Latanoprost reduced IOP by increasing C by 0.009 ± 0.0003 μL/min/mm Hg (P < 0.001), without affecting Fin or Fu. Betaxolol reduced Fin by 0.075 ± 0.021 μL/min (P = 0.009). Brimonidine increased C by 0.005 ± 0.0005 μL/min/mm Hg (P < 0.001) and Fu by 0.013 ± 0.003 μL/min (P = 0.007).


CONCLUSIONS
In this study, a unique technique was developed to concurrently assess IOP, C, Pe, Fin, and Fu in the mouse eye. This experimental approach should be useful to evaluate effects of pharmacologic agents or genetic manipulations on aqueous humor dynamics in mice and other animal models.
Millar
J Cameron
JC
Alcon Research, Ltd., Fort Worth, Texas 76134-2099, USA. cameron.millar@alconlabs.com
Clark
Abbot F
AF
Pang
Iok-Hou
IH
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage*; D001082:Aqueous Humor / Q000378:metabolism*; D015784:Betaxolol / Q000008:administration & dosage; D000068438:Brimonidine Tartrate; D004396:Coloring Agents; D003911:Dextrans; D016650:Fluorescein-5-isothiocyanate / Q000031:analogs & derivatives; D007429:Intraocular Pressure / Q000187:drug effects / Q000502:physiology*; D000077338:Latanoprost; D008297:Male; D008365:Manometry; D051379:Mice; D008807:Mice, Inbred BALB C; D011461:Prostaglandins F, Synthetic / Q000008:administration & dosage; D011810:Quinoxalines / Q000008:administration & dosage; D012590:Sclera / Q000378:metabolism*; D014065:Tonometry, Ocular; D014129:Trabecular Meshwork / Q000378:metabolism*; D014602:Uvea / Q000378:metabolism*; D014690:Venous Pressure
D000959:Antihypertensive Agents; D004396:Coloring Agents; D003911:Dextrans; D011461:Prostaglandins F, Synthetic; D011810:Quinoxalines; C015219:fluorescein isothiocyanate dextran; D000068438:Brimonidine Tartrate; D000077338:Latanoprost; D016650:Fluorescein-5-isothiocyanate; D015784:Betaxolol