Accelerated cataract formation and reduced lens epithelial water permeability in aquaporin-1-deficient mice.
OBJECTIVE
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 approximately 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.
Ruiz-Ederra
Javier
J
Department of Medicine , Cardiovascular Research Institute, University of California, San Francisco, California 94143-0521, USA.
Verkman
A S
AS
D000082:Acetaminophen / Q000633:toxicity; D000818:Animals; D051398:Aquaporin 1 / Q000172:deficiency / Q000502:physiology*; D001834:Body Water / Q000378:metabolism*; D002386:Cataract / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D004338:Drug Combinations; D004847:Epithelial Cells / Q000378:metabolism*; D005452:Fluoresceins / Q000378:metabolism; D015151:Immunoblotting; D007124:Immunoenzyme Techniques; D007908:Lens, Crystalline / Q000378:metabolism*; D008748:Methylcholanthrene / Q000633:toxicity; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic
C496021:Aqp1 protein, mouse; D004338:Drug Combinations; D005452:Fluoresceins; D051398:Aquaporin 1; C085925:calcein AM; D000082:Acetaminophen; D008748:Methylcholanthrene