Cataracts of many different etiologies are associated with oxidation of lens components. The lens is protected by maintenance of a pool of reduced glutathione (GSH) and other antioxidants. Because gap junction channels made of the lens connexins, Cx46 and Cx50, are permeable to GSH, we tested whether mice expressing two different mutants, Cx46fs380 and Cx50D47A, cause cataracts by impairing lens glutathione metabolism and facilitating oxidative damage. Levels of GSH were not reduced in homogenates of whole mutant lenses. Oxidized glutathione (GSSG) and the GSSG/GSH ratio were increased in whole lenses of Cx50D47A, but not Cx46fs380 mice. The GSSG/GSH ratio was increased in the lens nucleus (but not cortex) of Cx46fs380 mice at 4.5 months of age, but it was not altered in younger animals. Carbonylated proteins were increased in Cx50D47A, but not Cx46fs380 lenses. Thus, both mouse lines have oxidizing lens environments, but oxidative modification is greater in Cx50D47A than in Cx46fs380 mice. The results suggest that GSH permeation through lens connexin channels is not a critical early event in cataract formation in these mice. Moreover, because oxidative damage was only detected in animals with significant cataracts, it cannot be an early event in their cataractogenesis.
Keywords: GSH metabolism; cataracts; connexin; oxidative stress.