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.

PURPOSE: Kynurenic acid (KYNA), an endogenous tryptophan metabolite, is an N-methyl-D-aspartate (NMDA) antagonist active at the glycine-binding site of the NMDA-receptor complex. The authors investigated whether systemic administration of a biochemical precursor of KYNA, L-kynurenine (L-Kyn), could block NMDA- or kainic acid (KA)-induced cell death in adult rat retinal ganglion cells (RGCs) and protect NMDA-treated animals from lesion-induced visual deficits.
METHODS: Rats were injected with 20-nmol NMDA or 5-nmol KA intraocularly. To quantify the number of surviving RGCs, the retrograde tracer horseradish-peroxidase was injected into the superior colliculus contralateral to the lesioned eye. Surviving RGCs were counted on wholemounted retinae in a centroperipheral gradient, as well as in the four quadrants, using a computer-assisted image analysis system.
RESULTS: The NMDA-injections resulted in an approximately 82% RGC loss in the adult rat retina compared with control retinae and a cell loss of approximately 50% in KA-treated retinae. Pretreatment with L-Kyn significantly reduced NMDA-induced RGC degeneration to values of approximately 60%, but KA toxicity was not significantly affected by L-Kyn pretreatment. Intraocular injections of NMDA 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 significantly improved as compared with NMDA-treated rats.
CONCLUSIONS: These findings show that systemic administration of L-Kyn in adult rats can block NMDA-induced retinal ganglion cell death in vivo and preserves brightness discrimination performance.