Advanced glycation endproducts as UVA photosensitizers of tryptophan and ascorbic acid: consequences for the lens

Upon aging, the lens accumulates brown fluorophores, mainly derived from the Maillard reaction between vitamin C oxidation products and crystallins lysine residues. At the same time, the concentration of UVA filters decreases, allowing some radiation to be absorbed by lenticular advanced glycation endproducts (AGEs). This paper quantifies the photosensitizing activity of AGEs at various oxygen pressures, and compares it to that of lenticular riboflavin (RF). Solutions containing the sensitizer and the substrates tryptophan (Trp) and ascorbate (AH(-)) were irradiated at 365 nm. We show that the AGEs-photosensitized Trp oxidation rate increases with AGEs concentration and is optimal at 5% oxygen, the pressure in the lens. By contrast, for AH(-), the photooxidation rate increases with oxygen concentration. Despite the higher quantum yield of RF-depending reactions, its low concentration as compared to that of AGEs in aging lenses induces significantly higher Trp and AH(-) photodegradation rates with AGEs than with RF. As ascorbate is more rapidly photodegraded than Trp, the antioxidant competitively protects Trp from oxidation up to 1 mM, although not absolutely. We conclude that in the aging lens, AH(-) exerts a strong UVA protecting activity, but does not impede some Trp residue to be photodegraded proportionally to the AGEs concentration.