Evidence for Intraocular Synthesis of Kynurenic Acid, a Putative Endogenous Neuroprotectant

Kynurenic acid (KYNA), an excitatory amino acid antagonist preferentially active at glycine binding site of the NMDA receptor, has been previously identified in the brain. This study was designed to examine its presence in the rabbit vitreous humor. Mean (± SD) level of KYNA in the vitreous was 22.3 ± 3.9 pmol/ml as determined by HPLC. Intravitreal administration of 10 mmol aminooxyacetic acid (AOAA), a KYNA synthesis inhibitor, diminished its production by 9.6% after 2 h, 47.8% after 24 h and 21.5% after 48 h. It can be concluded that AOAA decreases the intravitreal concentration of KYNA, providing evidence of its intraocular origin.

[1]  A. Chiarugi,et al.  The kynurenine metabolic pathway in the eye: studies on 3‐hydroxykynurenine, a putative cataractogenic compound , 1999, FEBS letters.

[2]  V. Kapoor,et al.  Immuno‐localization of kynurenine aminotransferase (KAT) in the rat medulla and spinal cord , 1997, Neuroreport.

[3]  R. Schwarcz,et al.  Characterization of rat brain kynurenine aminotransferases I and II , 1997, Journal of neuroscience research.

[4]  J. Carver,et al.  Oxidation products of 3-hydroxykynurenine bind to lens proteins: relevance for nuclear cataract. , 1997, Experimental eye research.

[5]  M. Kreutz,et al.  Systemic L-kynurenine administration partially protects against NMDA, but not kainate-induced degeneration of retinal ganglion cells, and reduces visual discrimination deficits in adults rats. , 1996, Investigative ophthalmology & visual science.

[6]  S. Lipton,et al.  Chronic low-dose glutamate is toxic to retinal ganglion cells. Toxicity blocked by memantine. , 1996, Investigative ophthalmology & visual science.

[7]  R. Miller,et al.  The role of NMDA and non-NMDA excitatory amino acid receptors in the functional organization of primate retinal ganglion cells , 1994, Visual Neuroscience.

[8]  T. Stone,et al.  Neuropharmacology of quinolinic and kynurenic acids. , 1993, Pharmacological reviews.

[9]  R. Truscott,et al.  The modification of proteins by 3-hydroxykynurenine. , 1993, Experimental eye research.

[10]  R. Truscott,et al.  UV filters in human lenses: tryptophan catabolism. , 1993, Experimental eye research.

[11]  W. Turski,et al.  Aminooxyacetic acid produces excitotoxic lesions in the rat striatum , 1991, Synapse.

[12]  R. Schwarcz,et al.  Focal injection of aminooxyacetic acid produces seizures and lesions in rat hippocampus: Evidence for mediation by NMDA receptors , 1991, Experimental Neurology.

[13]  E. Cavalheiro,et al.  Seizures induced by aminooxyacetic acid in mice: Pharmacolgical characteristics , 1991, Synapse.

[14]  U. Ungerstedt,et al.  Determination of extracellular kynurenic acid in the striatum of unanesthetized rats: Effect of aminooxyacetic acid , 1990, Neuroscience Letters.

[15]  R. Schwarcz,et al.  Uptake of Kynurenine into Rat Brain Slices , 1990, Journal of neurochemistry.

[16]  T. Guilarte,et al.  Cytotoxicity of 3-hydroxykynurenine in a neuronal hybrid cell line , 1989, Brain Research.

[17]  R. Schwarcz,et al.  High-affinity uptake of L-kynurenine by a Na+-independent transporter of neutral amino acids in astrocytes , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[18]  R. Schwarcz,et al.  Rat Brain Slices Produce and Liberate Kynurenic Acid upon Exposure to l‐Kynurenine , 1989, Journal of neurochemistry.

[19]  G. Lombardi,et al.  Presence of Kynurenic Acid in the Mammalian Brain , 1988, Journal of neurochemistry.

[20]  R. Schwarcz,et al.  Identification and quantification of kynurenic acid in human brain tissue , 1988, Brain Research.

[21]  K. Shibata,et al.  Fluorimetric micro-determination of kynurenic acid, an endogenous blocker of neurotoxicity, by high-performance liquid chromatography. , 1988, Journal of chromatography.

[22]  Malcolm M. Slaughter,et al.  Excitatory amino acid receptors of the retina: diversity of subtypes and conductance mechanisms , 1986, Trends in Neurosciences.

[23]  J. Olney.  Inciting excitotoxic cytocide among central neurons. , 1986, Advances in experimental medicine and biology.

[24]  R. Schwarcz,et al.  Kynurenic acid blocks neurotoxicity and seizures induced in rats by the related brain metabolite quinolinic acid , 1984, Neuroscience Letters.