fructosyl-lysine and Cataract

Glycation, which begins with the spontaneous reaction between sugar and proteins by the formation of Schiff bases, is known to especially damage long-lived proteins such as lens crystallins, and has been implicated in the ageing process and particularly in cataract formation. In this study of human senile cataract, a specific method is used to measure the formation of Amadori compounds in control postmortem and cataractous lenses, but no difference was found. However, the fluorescence of proteins at 430 nm (exc 350 nm), which has been attributed to advanced glycation, increased with normal ageing of the lens (cortex versus nucleus, and as a function of subject's age for each type of fibres) and was further enhanced in cataractous lenses. The precise molecular origin of this fluorescence remains to be elucidated. In parallel to the accumulation of non-tryptophan fluorophores, a decrease in the membrane fluidity was observed with lens ageing and more acutely with cataract. Both parameters are positively correlated (P < 1%). The modification of the membrane structure with glycation could explain the strong permeability changes occurring during cataract, measured here in terms of cation concentration and inositol leakage, as shown by the negative relationship between the fluorescence signal and the sodium to potassium ratio or the inositol level.

Topics: Aged; Aged, 80 and over; Cataract; Crystallins; Glycosylation; Humans; Lens Cortex, Crystalline; Lens Nucleus, Crystalline; Lysine; Membrane Fluidity; Middle Aged; Spectrometry, Fluorescence

To assess the significance of glycation, nonenzymatic browning, and oxidation of lens crystallins in cataract formation in elderly diabetic patients, we measured three distinct products of glycation, browning, and oxidation reactions in cataractous lens crystallins from 29 diabetic patients (mean +/- SD age 72.8 +/- 8.8 yr) and 24 nondiabetic patients (age 73.5 +/- 8.3 yr). Compounds measured included 1) fructoselysine (FL), the first stable product of glycation; 2) pentosidine, a fluorescent, carbohydrate-derived protein cross-link between lysine and arginine residues formed during nonenzymatic browning; and 3) N epsilon-(carboxymethyl)lysine (CML), a product of autoxidation of sugar adducts to protein. In diabetic compared with nondiabetic patients, there were significant increases (P less than 0.001) in HbA1 (10.2 +/- 3.1 vs. 7.1 +/- 0.7%), FL (7.6 +/- 5.4 vs. 1.7 +/- 1.2 mmol/mol lysine), and pentosidine (6.3 +/- 2.8 vs. 3.8 +/- 1.9 mumol/mol lysine). The disproportionate elevation of FL compared with HbA1 suggests a breakdown in the lens barrier to glucose in diabetes, whereas the increase in pentosidine is indicative of accelerated nonenzymatic browning of diabetic lens crystallins. CML levels were similar in the two groups (7.1 +/- 2.4 vs. 6.8 +/- 3.0 mmol/mol lysine), providing no evidence for increased oxidative stress in the diabetic cataract. Thus, although the modification of lens crystallins by autoxidation reactions was not increased in diabetes, the increase in glycation and nonenzymatic browning suggests that these processes may acclerate the development of cataracts in diabetic patients.

Topics: Aged; Arginine; Cataract; Cataract Extraction; Crystallins; Diabetic Retinopathy; Female; Glycosylation; Humans; Lysine; Male