Cysteamine prevents the development of lens opacity in a rat model of selenite-induced cataract

Invest Ophthalmol Vis Sci. 2012 Mar 15;53(3):1452-9. doi: 10.1167/iovs.11-8636.

Abstract

Purpose: The activation of transglutaminase 2 (TG2) by oxidative stress through TGFβ has been reported to play a crucial role in cataract formation. The authors investigated whether TG2 is involved in selenite-induced cataract formation in rats and whether cysteamine, a chemical inhibitor of TG2, can prevent cataract formation in this model.

Methods: Intracellular TG2 activity was monitored in a human lens epithelial cell (HLE-B3) line and cultured rat lenses after treatment with selenite. Rat pups (13 days old) were injected subcutaneously with sodium selenite (Na(2)SeO(3); 20 μmol/kg) and intraperitoneally with cysteamine (30, 40, and 60 mg/kg) for 14 days. Lenses were evaluated photographically at days 7 and 14. The concentrations of malondialdehyde and glutathione in the lenses were determined.

Results: In HLE-B3 cells or rat lenses, selenite induced intracellular TG activity, which was inhibited by cysteamine. In selenite-treated rats, the rate of cataract formation was significantly reduced by cysteamine (P < 0.001). The mean cataract area in the lenses of cysteamine-treated rats was smaller than that of control rats (P < 0.01). The levels of total and reduced glutathione in the lenses of cysteamine-treated rats extracted at day 14 were higher than those of control rats.

Conclusions: Cysteamine suppresses cataract formation induced by selenite in rats, suggesting that cysteamine can be used as a pharmaceutical intervention to prevent or delay cataract formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Cataract / chemically induced
  • Cataract / enzymology
  • Cataract / prevention & control*
  • Cell Line
  • Cysteamine / pharmacology*
  • Disease Models, Animal
  • Enzyme Activation
  • Epithelial Cells / metabolism
  • Female
  • GTP-Binding Proteins / antagonists & inhibitors
  • GTP-Binding Proteins / metabolism*
  • Glutathione / metabolism
  • Humans
  • Lens, Crystalline / drug effects*
  • Lens, Crystalline / metabolism
  • Male
  • Protein Glutamine gamma Glutamyltransferase 2
  • Radiation-Protective Agents / pharmacology*
  • Rats
  • Rats, Sprague-Dawley
  • Sodium Selenite
  • Transglutaminases / antagonists & inhibitors
  • Transglutaminases / metabolism*

Substances

  • Radiation-Protective Agents
  • Tgm2 protein, rat
  • Cysteamine
  • Protein Glutamine gamma Glutamyltransferase 2
  • Transglutaminases
  • GTP-Binding Proteins
  • Glutathione
  • Sodium Selenite