Tryptophan-derived ultraviolet filter compounds covalently bound to lens proteins are photo sensitizers of oxidative damage

The human eye is chronically exposed to light of wavelengths > 300 nm. In the young human lens, light of wavelength 300-400 nm is predominantly absorbed by the free Trp derivatives kynurenine (Kyn), 3-hydroxykynurenine (30HKyn), and 3-hydroxykynurenine-O-beta-D-glucoside (30HKynG). These ultraviolet (UV) filter compounds are poor photosensitizers. With age, the levels of the free UV filters in the lens decreases and those of protein-bound UV filters increases. The photochemical behavior of these protein-bound UV filters and their role in UV damage are poorly elucidated and are examined here. UVA illumination of protein-bound UV filters generated peroxides (principally H2O2) in a metabolite-, photolysis-time-, and wavelength-dependent manner. Unmodified proteins, free Tip metabolites, and Trp metabolites that do not bind to lens proteins gave low peroxide yields. Protein-bound 30HKyn (principally at Cys residues) yielded more peroxide than comparable Kyn and 30HKynG adducts. Studies using D2O and sodium azide implicated O-1(2) as a key intermediate. Illumination of the protein-bound adducts also yielded protein-bound Tyr oxidation products (DOPA, di-tyrosine) and protein cross-links via alternative mechanisms. These data indicate that the covalent modification of lens proteins by Kyn derivatives yields photosensitizers that may enhance oxidation in older lenses and contribute to age-related nuclear cataract. (c) 2007 Elsevier Inc. All rights reserved.