Effect of Sorbitol on Alpha-Crystallin Structure and Function

Loss of eye lens transparency due to cataract is the leading cause of blindness all over the world. While aggregation of lens crystallins is the most common endpoint in various types of cataracts, chaperone-like activity (CLA) of alpha-crystallin preventing protein aggregation is considered to be important for maintaining the eye lens transparency. Osmotic stress due to increased accumulation of sorbitol under hyperglycemic conditions is believed to be one of the mechanisms for diabetic cataract. In addition, compromised CLA of alpha-crystallin in diabetic cataract has been reported. However, the effect of sorbitol on the structure and function of alpha-crystallin has not been elucidated yet. Hence, in the present exploratory study, we described the effect of varying concentrations of sorbitol on the structure and function of alpha-crystallin. Alpha-crystallin purified from the rat lens was incubated with varying concentrations of sorbitol in the dark under sterile conditions for up to 5 days. At the end of incubation, structural properties and CLA were evaluated by spectroscopic methods. Interestingly, different concentrations of sorbitol showed contrasting results: at lower concentrations (5 and 50 mM) there was a decrease in CLA and subtle alterations in secondary and tertiary structure but not at higher concentrations (500 mM). Though, these results shed a light on the effect of sorbitol on alpha-crystallin structure-function, further studies are required to understand the mechanism of the observed effects and their implication to cataractogenesis.

Automated summary

Cataract caused by the aggregation of lens crystallins is a major cause of blindness worldwide. The chaperone-like activity of alpha-crystallin plays a crucial role in maintaining lens transparency. Increased sorbitol accumulation due to hyperglycemia is believed to be a mechanism for diabetic cataract, but its effect on alpha-crystallin structure and function is not yet understood. In this exploratory study, different concentrations of sorbitol were found to have contrasting effects on alpha-crystallin, with lower concentrations leading to decreased chaperone-like activity and subtle structural changes. Further research is needed to understand the mechanisms and implications of these effects on cataractogenesis.