Evaluation of AL-05712 and AL-05741 as thioltransferase mimics for the prevention and recovery of pre-cataractous changes in lens

It has been previously shown that during the aging process, the human eye l ens accumulates protein-glutathione mixed disulfides (PSSG) and that the re duced glutathione (GSH) level drops. These changes become even more pronoun ced during cataractogenesis. In this report, the ability of AL-05712 and AL -05741 to lower PSSG and elevate GSH in three separate model systems was ev aluated. AL-05741 was able to decrease PSSG in the cell-free system by over 30% at a concentration of 0.1 mM. AL-05712, the ester form of AL-05741, de creased mixed disulfides by about 8% in the same system in the absence of a ny cellular esterases. Both compounds could partially inhibit the loss of G SH seen in the H2O2 control in cultured rat lenses and in addition, the acc umulation of PSSG was substantially decreased. Human lenses incubated in AL -05712 showed a significant elevation of cortical GSH and a decrease in PSS G in three of four sets of cultured human lenses.