SYSTEMIC L-KYNURENINE ADMINISTRATION PARTIALLY PROTECTS AGAINST NMDA,BUT NOT KAINATE-INDUCED DEGENERATION OF RETINAL GANGLION-CELLS, AND REDUCES VISUAL-DISCRIMINATION DEFICITS IN ADULT-RATS

Purpose. Kynurenic acid (KYNA), an endogenous tryptophan metabolite, i s an N-methyl-D-aspartate (NMDA) antagonist active at the glycine-bind ing site of the NMDA-receptor complex. The authors investigated whethe r svstemic administration of a biochemical precursor of KYNA, L-kynure nine (L-Kyn), could block NMDA- or kainic acid (KA)-induced cell death in adult rat retinal ganglion cells (RGCs) and protect NMDA-treated a nimals from lesion-induced visual deficits. Methods. Rats were injecte d with 20-nmol NMDA or 5-nmol KA intraocularly. To quantify the number of surviving RGCs, the retrograde tracer horseradish-peroxidase was i njected into the superior colliculus contralateral to the lesioned eye . Surviving RGCs were counted on wholemounted retinae in a centroperip heral gradient, as well as in the four quadrants, using a computer-ass isted image analysis system. Results. The NMDA-injections resulted in an approximately 82% RGC loss in the adult rat retina compared,vith co ntrol retinae and a cell loss of approximately 50% in KA-treated retin ae. Pretreatment with L-Kyn significantly reduced NMDA-induced RGC deg eneration to values of approximately 60%, but KA toxicity was not sign ificantly affected by L-Kyn pretreatment. Intraocular injections of NM DA resulted in an impairment of visual discrimination behavior, which partially recovered within a period of approximately 3 weeks. However, when treated systemically with L-Kyn, brightness discrimination was s ignificantly improved as compared with NMDA-treated rats. Conclusions. These findings show that systemic administration of L-Kyn in adult ra ts can block NMDA-induced retinal ganglion cell death in vivo and pres erves brightness discrimination performance.