Synthesis of Kynurenic Acid, a Tryptophan Derivative in Cataractous Lenses

Abstract

Abstract: : Purpose: Kynurenines and their glycoside derivatives absorb UV radiation, thus, they may be useful in protecting the retina from UV light. Kynurenine aminotransferases (KAT I and II) are pivotal for the synthesis of kynurenic acid (KYNA). The experiments were designed to investigate KYNA synthesis in human cataractous lenses and in experimental cataract in diabetic rats. Methods: KYNA levels were investigated with HPLC and detected fluorimetrically. Nuclei of human cataractous lenses collected following planned extracapsular extraction were classified accordingly to LOCS III and compared to clear lenses with regard to KYNA concentration. Cataractous lenses from STZ–treated rats were compared to controls. Immunohistochemistry was performed using polyclonal antibodies against KAT I or KAT II on human lenses. Results: In clear lenses (NC0), KYNA concentration was 0.95 ± 0.22, in NC1 was 0.8 ± 0.72, in NC2 was 1.18 ± 0.88, in NC3 was 1,31 ± 0.70, in NC4 was 1.78 ± 0.92, in NC5 was 8.80 ± 8.28 (P<0.05 vs NC0) and in NC6 was 14.0 ± 11.1 (P<0.05 vs NC0). Correlation between the grade of cataract (LOCS III scale) and KYNA concentration was noted (r=0.047, P<0.001). Elevated KYNA concentration in rat cataractous lenses was observed (P<0.05). Up–regulation of KAT I and KAT II expression depending on development of cataract was also noted. Conclusions: Elevation of KYNA levels and up–regulation of KAT I and II expression in cataractous lenses may suggest potential role of KYNA synthesis in mechanisms of cataract formation. R. Rejdak grant: QLK2–CT–2002–51562)

Keywords: cataract • pharmacology • protein modifications-post translational