Protein glycation and in vivo distribution of human lens fluorescence

Abstract

Glycated proteins formed by the Maillard reaction were measured by furosine determination in human normal lenses and in senile and diabetic cataracts. Furosine, an hydrolysis product of fructose-lysine adduct formed in the early stages of the Maillard reaction, was measured by high performance liquid chromatography (HPLC). Furosine levels in diabetic cataracts were found to be 3 to 4 times higher than those observed for senile cataracts. The increased glycation levels both in cortex and nucleus were related to the increase of fluorescence determined in vitro by fluorometry and in vivo by Scheimpflug photography. Lens proteins were incubated with glucose and it has been demonstrated that protein glycation occurred parallel with the increase in concentration of fluorescent chromophores that present similar characteristics as those observed in vivo. The results indicate that protein insolubilization seemed to involve preferentially glycated proteins and at least in diabetic cataracts, the process seems to be initiated in the cortical region.

Carbohydrate nutrition, glycemic index, and the 10-y incidence of cataract

“…region in diabetic cataract (33). Epidemiologic studies also support a more consistent link between diabetes and cortical rather than nuclear cataract (3,4,6,7).…”

“…Glucose is taken up relatively slowly from plasma into the aqueous humor, and then it passes freely into the lens, where it is slowly turned over (18). Prolonged exposure of the lens proteins to elevated glucose was observed to cause accumulation of polyol and glycation, which may then produce oxidation, cross-linking, aggregation, and precipitation of lens proteins (32)(33)(34)(35). Because peak blood glucose concentrations and average blood glucose concentrations (as assessed by area under the curve) are higher after high GI foods (11), it is conceivable that higher GI foods could produce more damage to lens tissue than do lower GI foods.…”

Glycated Serum Albumin and AGE Receptors

“…An interesting feature of fluorescence (and Raman spectroscopy, see Section 3.2.10) is that these measurements can be performed in a noninvasive manner. For example, the AGE-related fluorescence of skin and the eye lens have been measured [132][133][134][135][136]. Interestingly, AGE-related fluorescence of the human skin has been correlated with vascular complications [137], renal function [132,138,139], diabetes [140], obesity [141], and even mental disorders [142].…”

A Technical Approach to the Evaluation of Glucose Oxidation: Implications for Diabetic Cataract

“…Another hypothesis, involving direct chemical damage induced by glucose, was based on the assump tion that exposure of proteins to hyperglyce mia would favor its degradation through a Mailllard type reaction [28,33], Such a mech anism. producing fluorescent chromophores as late products, would account for the high lens fluorescence levels detected in human diabetic cataracts [27,33], It is however nowclear that most of the fluorophores found in human lenses including pentosidine may orig inate efficiently from glucose, fructose and even ascorbate by a sequence of transitionmetal-catalyzed oxidation and decarboxyla tion reactions [34], It has further been suggest ed that monosaccharides can enolize and re duce molecular oxygen under physiological conditions yielding a-ketoaldchydcs, fFCT and free radical intermediates [7], We have now shown that bovine lens membranes are prone to oxidize in the presence of glucose and trace amounts of transition metals. Fur thermore, both the glucose concentration and the incubation time used in our studies are significantly lower as compared to those used in typical nonenzvmatic glycation studies [27,35].…”

“…In the last few years, many studies in dif ferent laboratories have associated premature cataract development in diabetes with the chronic exposure to abnormally high glucose concentrations [27,28]. Initially the most widely accepted mechanisms included the formation of osmotic active substances, such as sorbitol, resulting from the activation of alternative metabolic pathways including the activation of the enzyme aldose reductase [29][30][31].…”