Methylglyoxal-derived modifications in lens aging and cataract formation.

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Abstract

PURPOSE: To determine whether the Maillard reaction of methylglyoxal is associated with human lens aging and cataractogenesis and to investigate how glutathione depletion affects methylglyoxal-derived modifications in organ-cultured lenses. METHODS: Antibodies against methylglyoxal-derived modifications were developed in rabbits and purified by immunoaffinity chromatography. A competitive enzyme-linked immunosorbent assay (ELISA) measured methylglyoxal-derived products in human lens proteins. Lenses of galactosemic rats grown in organ culture were used to assess the role of glutathione-dependent pathways in methylglyoxal metabolism and Maillard reactions. RESULTS: Methylglyoxal-derived modifications in the human lens were age dependent, and brunescent lenses had the highest levels of these modifications. Immunofluorescence staining identified antigens distributed throughout the lens, with higher levels in old lenses than in younger ones. Experiments with normal or galactosemic rat lenses grown in organ culture showed that lens proteins do not have an increase in methylglyoxal-modified proteins when cultured in medium containing 500 microM methylglyoxal alone, but they accumulate modified proteins when cultured with DL-glyceraldehyde. Inclusion of 30 mM glucose in the medium marginally increased methylglyoxal-derived products, but there was no correlation between lens glutathione content and methylglyoxal-derived modifications. CONCLUSIONS: Methylglyoxal-mediated Maillard reactions that occur in the human lens may play a role in lens aging and cataract formation. Methylglyoxal is probably derived from metabolic pathways within the lens. Decreased glutathione in organ-cultured rat lenses does not significantly influence methylglyoxal-mediated Maillard reactions.