Factors affecting the survival of cat retinal ganglion cells after optic nerve injury.
After partial transection of one optic nerve in adult cats the majority of beta retinal ganglion cells degenerate and die 1 week after axotomy, whilst other cell classes degenerate slowly and survive for a long period after the lesion. We have investigated the effects of intravitreal and intraperitoneal injections of MK-801, a NMDA-glutamate receptor antagonist, on the early degeneration of retinal ganglion cells after partial optic nerve section. Control animals received saline intravitreal injections. Retinal flat mounts were retrogradely labelled with horseradish peroxidase and counterstained with Cresyl Violet. We evaluated the ganglion cell loss in the three experimental groups 1 week after lesion and compared them with normal uninjured controls and injured untreated retinae. In untreated retinae 49% of ganglion cells die 1 week after the lesion. Systemic MK-801 or saline prolonged survival of 41% of retinal ganglion cells that would die without treatment. Intravitreal MK-801 or saline prolonged survival of 71% of retinal ganglion cells that would die without treatment, but the results of saline administration had a larger range of variability. In untreated retinae many pyknotic cells were observed. They decreased in number after systemic MK-801 treatment and in some retinae treated with intravitreal injections of saline solution. There were no pyknotic cells after local, intravitreal MK-801 treatment. These results support the hypothesis that NMDA-receptor mediated neurotoxicity plays an important role in the early retinal ganglion cell death after retrobulbar axotomy. They also support the existence of an endogenous source of neurotrophins whose release is triggered by eyeball injury. We conclude that the early death of beta retinal ganglion cells after axotomy occurs by a mechanism that can be controlled by neurotrophins and antagonists to NMDA-glutamate receptors.
Russelakis-Carneiro
M
M
Departamento de Fisiologia, Universidade Federal do Pará, Brasil.
Silveira
L C
LC
Perry
V H
VH
D000818:Animals; D002415:Cats; D002470:Cell Survival / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006651:Histocytochemistry; D006735:Horseradish Peroxidase; D008297:Male; D009410:Nerve Degeneration; D020221:Optic Nerve Injuries; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012165:Retinal Ganglion Cells / Q000166:cytology / Q000187:drug effects*
D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D006735:Horseradish Peroxidase