title: Aquaporin deletion in mice reduces intraocular pressure and aqueous fluid production.
abstract: Aquaporin (AQP) water channels are expressed in the eye at sites of aqueous fluid production and outflow: AQP1 and AQP4 in nonpigmented ciliary epithelium, and AQP1 in trabecular meshwork endothelium. Novel methods were developed to compare aqueous fluid dynamics in wild-type mice versus mice lacking AQP1 and/or AQP4. Aqueous fluid production was measured by in vivo confocal microscopy after transcorneal iontophoretic introduction of fluorescein. Intraocular pressure (IOP), outflow, and anterior chamber compliance were determined from pressure measurements in response to fluid infusions using micropipettes. Aqueous fluid volume and [Cl(-)] were assayed in samples withdrawn by micropipettes. In wild-type mice (CD1 genetic background, age 4-6 wk), IOP was 16.0 +/- 0.4 mmHg (SE), aqueous fluid volume 7.2 +/- 0.3 microl, fluid production 3.6 +/- 0.2 microl/h, fluid outflow 0.36 +/- 0.06 microl/h/mmHg, and compliance 0.036 +/- 0.006 microl/mmHg. IOP was significantly decreased by up to 1.8 mmHg (P < 0.002) and fluid production by up to 0.9 microl/h in age/litter-matched mice lacking AQP1 and/or AQP4 (outbred CD1 and inbred C57/bl6 genetic backgrounds). However, AQP deletion did not significantly affect outflow, [Cl(-)], volume, or compliance. These results provide evidence for the involvement of AQPs in intraocular pressure regulation by facilitating aqueous fluid secretion across the ciliary epithelium. AQP inhibition may thus provide a novel approach for the treatment of elevated IOP.
authors.affiliation: Department of Medicine and Physiology, Cardiovascular Research Institute, 1246 Health Sciences East Tower, University of California at San Francisco, San Francisco, CA 94143, USA.
authors.forename: Duo
authors.initials: D
authors.lastname: Zhang
authors.forename: L
authors.initials: L
authors.lastname: Vetrivel
authors.forename: A S
authors.initials: AS
authors.lastname: Verkman
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D051398:Aquaporin 1; D051401:Aquaporin 4; D020346:Aquaporins / Q000235:genetics* / Q000378:metabolism*; D001082:Aqueous Humor / Q000378:metabolism*; D003187:Compliance; D007429:Intraocular Pressure / Q000502:physiology*; D051379:Mice; D018345:Mice, Knockout; D014867:Water / Q000378:metabolism
chemical_list: C496021:Aqp1 protein, mouse; C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D020346:Aquaporins; D014867:Water; D051398:Aquaporin 1