Indoleamine 2,3-dioxygenase in the human lens, the first enzyme in the synthesis of UV filters

Tryptophan-derived UV filters have recently been shown to bind to human len s proteins. These UV filter adducts increase in amount with age and appear to be mainly responsible for the yellowing of the lens in man. On the basis of research performed in other tissues, it has been assumed that indoleami ne 2,3-dioxygenase (IDO) may be the first and probably rate-limiting enzyme in UV filter biosynthesis. In this study, 25 human lenses were examined by a reliable and sensitive assay method with a monoclonal antibody specific for IDO. IDO activity was detected in all lenses ranging From 26 to 80 year s, and there was no clear relationship of IDO activity with age. The mean a ctivity was 0.85 +/- 0.49 nmol of kynurenine formed hr(-1) per lens. IDO ex pression was found to be localized in the anterior cortex of the lens with little or no activity in the posterior cortex or nucleus. The level in the iris/ciliary body was negligible (< 0.05 nmol of kynurenine formed hr(-1)). The lens IDO activity is consistent with UV Biter turnover values obtained previously These findings indicate that IDO is the first enzyme in the UV filter pathway and that UV filter biosynthesis is active even in aged lense s. Yellowing of the aged lens may therefore be preventable by drug-induced suppression of lens IDO activity. (C) 2001 Academic Press.