Major changes in human ocular UV protection with age

PURPOSE. Age-dependent human lens coloration may be explained by the bindin g of UV filters to crystallins. It has been proposed that glutathione may c ompete for reaction with UV filter degradation products and therefore prote ct crystallins from modification. To understand this process, UV filters we re quantified together with oxidized and reduced glutathione in human lense s of varying age. METHODS. Lens tissues were homogenized in ethanol to extract the UV filters . Metabolites were quantified by HPLC and correlations between them in the nuclear and cortical regions of the lens were examined. RESULTS. The concentrations of the UV filters 3-hydroxykynurenine, kynureni ne, and 3-hydroxykynurenine glucoside decreased linearly with age, with sli ghtly lower levels in the nucleus than the cortex. 4-(2-Amino-3-hydroxyphen yl)-4-oxobutanoic acid glucoside was found in higher levels in the nucleus than the cortex and decreased slowly in both regions with age. Glutathionyl -3-hydroxykynurenine glucoside was present in higher concentrations in the nucleus, barely detectable in young lenses, but increased significantly aft er age 50. Reduced glutathione levels were lower in the nucleus and decreas ed in both regions with age, yet oxidized glutathione increased in the nucl eus but remained constant in the cortex. CONCLUSIONS. Results are consistent with a predominantly nuclear origin for both 4-(2-amino-3-hydroxyphenyl)-4-oxobutanoic acid glucoside and glutathi onyl-3-hydroxykynurenine glucoside. This is in accord with their proposed m echanism of formation, which involves an initial deamination of 3-hydroxyky nurenine glucoside. This process is more pronounced in older lenses, possib ly because of the barrier to diffusion. The barrier may also explain the in crease in nuclear oxidized glutathione that is observed with age.