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R.A. Rejdak, F. Schuattauf, Y. Shenk, T. Zarnowski, P. Grieb, W.A. Turski, Z. Zagorski, K. Kohler, E. Zrenner; Alterations of Kynurenic Acid (KYNA) Formation in the Retina of DBA/2J Mice . Invest. Ophthalmol. Vis. Sci. 2003;44(13):106.
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Purpose: The DBA/2J mouse is a promising animal model of glaucoma. Mice of this strain spontaneously develop age-dependent RGC loss. Kynurenic acid (KYNA) is the only known endogenous glutamate receptor antagonist and it is synthesised in the retina by two kynurenine aminotransferases (KAT I and KAT II) (Rejdak et al. 2001, 2002). In the present study we therefore examined changes of KYNA content in response to RGC loss in the retina of DBA/2J mice. Methods: Retinas were obtained from 3, 6, 8 and 11 months old DBA/2J mice. Retinas from Bl6 mice were used as a control. Immunohistochemistry was performed on retinal sections using specific antibodies against KAT I, KAT II and glutamine synthetase as a marker for Müller cells. Retinal KYNA content was measured with HPLC. Spontaneous RGC death and accompanying phenomena were examined electron microscopically. Results: Double labelling studies showed that KAT I was expressed on Müller cell endfeet while KAT II was observed both on RGC and Müller cell endfeet in the mice retina. The expression of both KAT I and KAT II was markedly reduced in the retina of DBA/2J mice during ageing. KYNA content decreased significantly (p=0.03) in the retina of 6 month old DBA/2J mice and continued to decrease (p=0.008) in the retina of 11 months old animals when compared to age matched controls. Electron microscopy showed pronounced signs of RGC apoptosis, neoangiogenesis and swelling of Müller glia in the retina of 6 and 11 months DBA/2J mice. Conclusion: Our data show that apoptosis is the major mechanism of RGC death in DBA/2J mice. The KYNA content decreases in the retina of DBA/2J mice during ageing in response to RGC loss. It is therefore conceivable that KYNA deficiency is causally related to the pathology of neurodegenerative retinal diseases.
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