The efficacy of aldose reductase inhibitor, antioxidant butylated hydroxytoluene and cysteine protease inhibitor E64 on hyperglycemia-induced metabolic changes in the organ-cultured bovine lens.

It is well known that polyol related sugar cataract formation is preventable with aldose reductase inhibitor (ARI) and newly developed different kinds of ARIs have been extensively studied for potential clinical use. The potency of AD-5467 ARI (Takeda) on hyperglycemic lenses was evaluated by measuring of phosphate metabolites in phosphorus-31, (31P) nuclear magnetic resonance (NMR) spectra. Moreover, the effects of antioxidant butylated hydroxytoluene (BHT) and cysteine protease inhibitor E64 on hyperglycemic lenses were evaluated for comparative study, since some studies showed that these agents also possess the delay or preventive effects in sugar cataractogenesis. The lenses were dissected out from bovine eyes and incubated in Dulbeco's modified Eagles (DME) media containing 5.6 mM and 40 mM glucose with or without the ARI, BHT, E64 for 24 hours. These were assessed by MNR spectrometer operating at 109.25 MHz for 31P. The morphologic changes of the lenses were revealed by histologic and ultrastructural examinations. The lenses incubated in high glucose medium showed significant decreased levels of adenosine triphosphate (ATP), associated with increased inorganic phosphates and sugar phosphates levels. The lenses treated with ARI or E64 showed 70% to 80% protection of ATP levels and those with BHT showed 100% protection of ATP levels. These results indicated that sugar catractogenesis is multifactorial process in which the other mechanisms are also involved besides the polyol pathway mechanism.