The roles of glutathione reductase and γ-glutamyl transpeptidase in corneal transendothelial fluid transport mediated by oxidized glutathione and glucose

Abstract

Complete inhibition of corneal endothelial glutathione reductase by 1, 3-bis-(2-chloroethyl)-1-nitrosourea has been shown to be without effect on the endothelial fluid pump maintained by perfusion with either 0·10 m m -oxidized glutathione or 5·0 m m -glucose. Some dependence of pump function on γ-glutamyl transpeptidase is indicated by the 33% reduction in the amount of stromal deturgescence that was achieved by co-perfusion of GSSG with the transpeptidase inhibitor, 6-diazo-5-oxo- l -norleucine. The apparent 22% improvement in pump function found by coperfusion of glucose with 6-diazo-5-oxo- l -norleucine is likely the result of a reduced leak effected by reaction of the inhibitor with functional groups on the membrane. Endothelial levels of total glutathione after 3-hr perfusion periods with either glucose or oxidized glutathione were not statistically different, but a shift of the redox state of glutathione occurred in oxidized glutathione-perfused endothelia that resulted in a 4-fold increase in the cellular content of oxidized glutathione relative to that maintained by glucose. This and others' results are interpreted to indicate that glutathione is taken up by the endothelium and that oxidized glutathione is the privileged redox state for this process.