Increased levels of advanced glycation end products in human cataractous lenses

Abstract

Purpose To investigate the occurrence of advanced glycation end products (AGEs) formed oxidatively (pentosidine and N ϵ-carboxymethyl lysine [CML]) or nonoxidatively (imidazolone) in human lenses and the relation of AGEs to lens coloration, cataract type, and patients’ diabetic state. Setting Departments of Ophthalmology and Internal Medicine III, University of Jena, Jena, Germany. Methods Pentosidine, CML, and imidazolone concentrations were measured in the water-soluble protein fraction of 44 cataractous lenses (from 24 nondiabetic and 20 diabetic donors) and 6 noncataractous control lenses. Results Pentosidine, CML, and imidazolone were higher in cataractous lenses than in control lenses (pentosidine, 3.7 pmol/mg ± 5.3 (SD) and 1.9 ± 1.7 pmol/mg, respectively; CML, 3.0 ± 2.2 nmol/mg and 1.3 ± 0.7 nmol/mg, respectively; imidazoline, 80.4 ± 93.3 AU/mg and 19.6 ± 18.5 AU/mg, respectively). Among the cataractous lenses, the highest AGE concentrations were found in mature cataracts, with a statistically significant increase in CML. The AGE content increased relative to the intensity of brown coloration of the lens; the brown coloration also indicated the highest rise of imidazolone compared to pentosidine and CML. Lenses from diabetic donors had generally similar pentosidine values and elevated CML and imidazolone levels compared to lenses from nondiabetic donors. The pentosidine, CML, and imidazolone levels in the lenses correlated significantly with one another but not with patient age. Conclusions Advanced glycation end products formed oxidatively and nonoxidatively occurred to a higher degree in cataractous lenses than in noncataractous lenses. The strong relationship between the lenses’ AGE content, color/opacity, and the state of the cataract may indicate that advanced glycation plays a pivotal role in cataract formation.