UV Filters in Human Lenses: Tryptophan Catabolism

Abstract

Primate lenses are unique in that they convert tryptophan (trp) into 3-hydroxykynurenine glucoside (30HKG). This is the major short-wave absorbing pigment present in human lenses and it may play a role in protecting the eye from UV-induced photodamage. A study has been performed on aspects of this metabolic pathway in human lenses. A significant rate of synthesis could be observed in a 24-hr period using intact lenses to which radiolabelled tryptophan had been added. Label was found in kynurenine (Kyn), 3-hydroxykynurenine (30HKyn) and 30HKG, although always to the greatest extent in the latter metabolite. Considerable variation in the proportion of label incorporated into 30HKG was observed. Older lenses tended to accumulate a greater percentage into the glucoside; the data indicating a generally greater flux throught the trp catabolic pathway in lenses above 60 years of age. Pulse-chase experiments on lens pairs suggested that there may be a significant loss or metabolism of 30HKG. Biosynthesis of 30HKG was found to take place in the lens epithelial cells. A linear rate of 30HKG efflux from organ cultured lenses was observed indicating that one pathway for removal of this compound involves diffusion through the lens capsule. That this pathway also occurs in vivo was confirmed by analysing samples of human vitreous humour. Based on efflux rates from cultured lenses (1·07 × 10 -3 ± 0·293 × 10 -3 ümol hr -1 n = 5), half-life values for 30HKG in the lens ranging between 7 and 40 hr were calculated. Since the concentration of 30HKG was found to be constant throughout the lens, a model is proposed in which the UV filter substance is synthesized in the epithelial zone, diffuses freely through the lens body and effluxes from the lens into the vitreous. This efflux appears to be the major route for removal of 30HKG from the lens. A marked age-related decrease in the lenticular level of 30HKG was observed. This was closely correlated with a drop in the level of 3-hydroxykynurenine, indicating that the decrease in concentration of the major human lens UV filter compound with age is not due to an alteration in glucosylation but may be the result of a fundamental change in lenticular trp catabolism with age.