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Javier Ruiz-Ederra, A. S. Verkman; Accelerated Cataract Formation and Reduced Lens Epithelial Water Permeability in Aquaporin-1-Deficient Mice. Invest. Ophthalmol. Vis. Sci. 2006;47(9):3960-3967. doi: 10.1167/iovs.06-0229.
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purpose. To investigate the involvement of aquaporin (AQP)-1 in lens epithelial cell water permeability and maintenance of lens transparency in experimental models of cataract formation.
methods. Comparative studies were performed on wild-type versus AQP1-null mice. Osmotic water permeability was measured in calcein-stained epithelial cells in intact lenses from fluorescence changes in response to osmotic gradients. Lens water content was measured by gravimetry using kerosene–bromobenzene density gradients, and from wet/dry weight measurements. Lens transparency was measured by contrast analysis of transmitted grid images. Cataract formation was induced in vitro by incubation in high-glucose solutions and in vivo by acetaminophen toxicity.
results. Immunofluorescence showed AQP1 expression in wild-type mice in epithelial cells covering the anterior surface of the lens. AQP1 deletion did not alter baseline lens morphology or transparency, though basal water content was ∼3% greater (P < 0.001). AQP1 deficiency reduced plasma membrane water permeability in lens epithelium by 2.8 ± 0.3-fold (P < 0.0001). Loss of lens transparency was accelerated by more than 50-fold in AQP1-null lenses bathed in a 55-mM glucose solution for 18 hours. At 4 hours after acetaminophen administration in 3-methylcholantrene–treated mice, lens opacification was seen in none of the six wild-type mice and in six of six AQP1-null mice.
conclusions. Lens AQP1 facilitates the maintenance of transparency and opposes cataract formation.
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