Evidence of a glycemic threshold for the development of cataracts in diabetic rats

Purpose. This study was aimed to establish a possible correlation between t he levels of plasma glucose and degree of lens opacification. Levels of gly cation- and glycoxidation-products in different lens protein fractions were also estimated with an aim to determine the involvement of these products in lens opacification. Methods. A wide range of hyperglycemia was induced by injecting different d oses of streptozotocin to 1 month old rats and lenses were examined on the 75(th), 90(th) and 150(th) day post-injection. Lens opacification was measu red by Scheimpflug imaging and densitometry. Levels of plasma glucose and g lycated hemoglobin were measured after overnight fasting. On 90(th) day, le vels of Amadori products in lens water soluble (WS) fraction were measured by affinity chromatography. Similarly, advanced glycation end products (AGE s) in lens WS, urea soluble (US) and alkali soluble (AS) fractions were mea sured immunochemically using a monoclonal antibody against the major glycox idation product, carboxymethyl lysine (CML). Results. Different dosages of streptozotocin injection resulted in a broad range of plasma glucose levels in the rats which were grouped into three gr oups on the basis of their plasma glucose levels: mildly diabetic (< 170 mg /dl plasma glucose), moderately diabetic (190-350 mg/dl) and severely diabe tic (> 400 mg/dl). On the 75(th), 90(th) and 150(th) day postinjection, onl y the moderately and severely diabetic rats developed cataracts whereas len ses of the mildly diabetic rats remained clear. As seen on 90(th) day, leve ls of glycated hemoglobin and Amadori products in lens WS fraction increase d significantly in the moderately and severely diabetic groups whereas in t he mildly diabetic rats these levels remained more or less same as in the c ontrol group. Levels of CML in WS fractions remained unchanged between cont rol rats and different diabetic groups, while US fractions showed a decreas e in CML in both the moderately and severely diabetic groups compared to th e controls and the mildly diabetic group. Interestingly, AS fractions conta ined the highest level of CML; the moderately and severely diabetic groups showed about 2-fold higher levels than the controls and the mildly diabetic group. Conclusions. This study strongly supports the existence of plasma glycemic threshold above which incidence of diabetic cataract formation increases ex ponentially. This threshold level seems to be at similar to 180 mg/dl or 10 mM plasma glucose. Significant increase in the levels of glycation and gly coxidation products mainly in cataract lenses suggests that glycation and g lycation-mediated oxidation play an important role in the development of di abetic cataracts.