Role of crystallins in diabetic complications

Abstract

Background: Crystallins are the major structural proteins of vertebrate eye lens responsible for maintaining the refractive index of the lens. However, recent studies suggest that they also have a functional significance in non-lenticular tissues. Prolonged uncontrolled diabetes results in the development of macro and microvascular complications that are the leading causes of morbidity and mortality in diabetic patients all over the world.

Scope of review: Recent studies have shown that crystallins play an instrumental role in diabetes and its complications. Therefore, this review highlights the current data on the impact of chronic hyperglycemia on expression, distribution, glycation, phosphorylation, chaperone-like function and, anti-apoptotic activity of crystallins. Furthermore, we discussed the insights for developing therapeutic strategies for diabetic complications including natural agents, peptides, and pharmacological chaperones that modulate or mimic chaperone activity of α-crystallins.

Major conclusions: Upregulation of crystallins appears to be a common feature of chronic diabetes. Further, chronic hyperglycemia induces the glycation and phosphorylation of crystallins, mainly α-crystallins and thereby alters their properties. The disturbed interaction of αB-crystallin with various apoptotic mediators including Bax and caspases is also an important factor for increased cell death in diabetes. Numerous dietary agents, peptides, and chemical chaperones prevent apoptosis and the loss of chaperone activity in diabetes.

General significance: Understanding the role of crystallins will aid in developing therapeutic strategies for alleviating pathophysiological conditions such as protein aggregation, inflammation, oxidative stress and apoptosis associated with chronic complications of diabetes including cataract, retinopathy, and cardiomyopathy. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.

Keywords: Apoptosis; Chaperone-like activity; Crystallin; Glycation; Hyperglycemia; Phosphorylation.