The structural alteration and aggregation propensity of glycated lens crystallins in the presence of calcium: Importance of lens calcium homeostasis in development of diabetic cataracts

• The imbalance of the calcium homeostasis has been indicated in the lenticular tissues of diabetic patients.
• Glycated crystallins indicate significant resistance against calcium-induced structural insults and aggregation.
• Glycated crystallins display markedly reduced calcium binding capacity.
• Glycation may significantly reduce calcium buffering capacity of lens crystallins.
• Poor calcium binding by these proteins may participate in the pathogenesis of diabetic cataracts.

The imbalance of the calcium homeostasis in the lenticular tissues of diabetic patients is an important risk factor for development of cataract diseases. In the current study, the impact of elevated levels of calcium ions were investigated on structure and aggregation propensity of glycated lens crystallins using gel electrophoresis and spectroscopic assessments. The glycated proteins indicated significant resistance against calcium-induced structural insults and aggregation. While, glycated crystallins revealed an increased conformational stability; a slight instability was observed for these proteins upon interaction with calcium ions. Also, in the presence of calcium, the proteolytic pattern of native crystallins was altered and that of glycated protein counterparts remained almost unchanged. According to results of this study it is suggested that the structural alteration of lens crystallins upon glycation may significantly reduce their calcium buffering capacity in eye lenses. Therefore, under chronic hyperglycemia accumulation of this cataractogenic metal ion in the lenticular tissues may subsequently culminate in activation of different pathogenic pathways, leading to development of lens opacity and cataract diseases.

During chronic hyperglycemia, the reduction in calcium binding capacity of glycated lens crystallins may participate in the pathogenesis of diabetic cataracts.Figure optionsDownload as PowerPoint slide