Accelerated cataract formation and reduced lens epithelial water permeability in aquaporin-1-deficient mice

Invest Ophthalmol Vis Sci. 2006 Sep;47(9):3960-7. doi: 10.1167/iovs.06-0229.


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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetaminophen / toxicity
  • Animals
  • Aquaporin 1 / deficiency
  • Aquaporin 1 / physiology*
  • Body Water / metabolism*
  • Cataract / chemically induced
  • Cataract / metabolism
  • Cataract / physiopathology*
  • Drug Combinations
  • Epithelial Cells / metabolism*
  • Fluoresceins / metabolism
  • Immunoblotting
  • Immunoenzyme Techniques
  • Lens, Crystalline / metabolism*
  • Methylcholanthrene / toxicity
  • Mice
  • Mice, Knockout
  • Mice, Transgenic


  • Aqp1 protein, mouse
  • Drug Combinations
  • Fluoresceins
  • Aquaporin 1
  • calcein AM
  • Acetaminophen
  • Methylcholanthrene