Diabetes-induced oxidative stress and cataract development and preventive role of antioxidant defense mechanism

Diabetes-associated oxidative stress results in mass production of different oxidative agents in the lenticular tissues, including hydrogen peroxide and peroxynitrite (PON), as well as the most potent glycating agent methylglyoxal (MGO). During chronic hyperglycemia, these highly reactive molecules and causative players in development of diabetic cataracts, induce important structural damages in a great variety of sensitive molecules of the lenticular tissues including crystallin proteins. On the other hand, eye lenses possess a powerful antioxidant defense mechanism, protecting various molecules against glycooxidation. The balance between oxidative/glycative agents and antioxidant defense mechanism is highly important for the protection against structural damages of eye lens proteins and other sensitive molecules of the lenticular tissues. However, during chronic hyperglycemia in diabetic patients this balance will alter in favor of the damaging molecules. The current investigation was aimed to study the effects of hydrogen peroxide, peroxynitrite and MGO on the structural and functional properties of lens crystallins using various spectroscopic methods and SDS-PAGE analysis. Modification of the lens proteins by PON and MGO led to the remarkable structural damages and crosslinking. Also, R12C and R54C mutant αA-crystallins indicated significant alteration in their structure, stability and chaperone activity upon incubation with H2O2 and PON, respectively. Additionally, ascorbic acid, glutathione and N-acetylcysteine revealed a significant preventive function against the structural damage of lens crystallins which induced by the reactive metabolites. Overall, our study highlights the protective functions of naturally occurring and therapeutic antioxidants against the structural damages of lens proteins which may occur during chronic hyperglycemia in diabetic patients.

Keywords:

Lens crystallins , Cataract , Hyperglycemia , Chaperone activity , Antioxidants