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.
OBJECTIVE
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.
Vorwerk
C K
CK
Institute of Medical Psychology, Medical Faculty, Otto-von-Guericke-University of Magdeburg, Germany.
Kreutz
M R
MR
Dreyer
E B
EB
Sabel
B A
BA
D000818:Animals; D001522:Behavior, Animal; D001692:Biological Transport; D002452:Cell Count; D016923:Cell Death / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006735:Horseradish Peroxidase / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007608:Kainic Acid / Q000633:toxicity*; D007737:Kynurenine / Q000494:pharmacology*; D008027:Light; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051381:Rats; D012162:Retinal Degeneration / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D012165:Retinal Ganglion Cells / Q000187:drug effects* / Q000502:physiology; D014786:Vision Disorders / Q000139:chemically induced / Q000503:physiopathology / Q000517:prevention & control*; D014796:Visual Perception / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D007737:Kynurenine; D016202:N-Methylaspartate; D006735:Horseradish Peroxidase; D007608:Kainic Acid