Evidence for Kynurenic Acid Synthesis in the Inner Retina During Ontogeny

Abstract

Abstract: : Purpose: The tryptophan metabolite kynurenic acid (KYNA) is the only known endogenous glutamate receptor antagonist and neuroprotectant. Kynurenine aminotransferases (KATs I and II) are responsible for the KYNA biosynthesis in mammalian cells. After proof of the presence of KYNA and KATs in the adult rat retina (Rejdak et al, NeuroReport,12: 3675, 2001) this study is the first to examine KYNA content and cellular immunolocalisation of KAT isoforms in the rat retina during ontogeny. Methods: Retinae from Brown Norway rats at different developmental stages between embryonic day 20 (E20) and the adult stages were used. KYNA levels were investigated with HPLC according to the method of Turski et al. (Brain Res 28:164, 1988). Immunohistochemistry was performed using polyclonal anti-KAT I antibody or polyclonal anti-KAT II antibody, generated by Okuno et al (Brain Res 534: 37, 1990 and 542: 307, 1991). Results: As determined by HPLC, KYNA was present in the retina during ontogeny. The mean (± SE) concentration of KYNA found in the embryonic rat retina (E20) was 95 10 pmol/ g wet wt and sharply increased within three days reaching a peak at birth (P0) of 702 77 pmol/g wet wt. At the end of the second postnatal week KYNA content decreased to 211 29 pmol/ g wet wt. A further decrease was observed subsequently with KYNA levels of 100 24.6 at 3 month and 58 4 pmol/g wet wt at 12 month. Immunohistochemical experiments showed that both KATs were present in the retina. KAT I was preferentially localised on Müller cell endfeet while KAT II was expressed in retinal ganglion cells. Conclusion: KYNA is present and synthesised in the inner retina during ontogeny. The high concentrations of KYNA during the first postnatal week suggest that KYNA may play an important neuromodulatory role in the retina during development. Supported by a guest scientist stipend of SFB 430 of the German Research Council and by the German Ophthalmologic Society.

Keywords: 556 retina: neurochemistry • 402 excitatory neurotransmitters • 434 immunohistochemistry