Excitotoxicity can be mediated through an interaction within the optic nerve; activation of cell body NMDA receptors is not required.
Axonal trauma leads to a series of pathologic events that can culminate in neuronal death. Although the precise mechanisms of retinal ganglion cell death after optic nerve crush in the rat model have not been elucidated, glutamate antagonists can protect retinal ganglion cells after optic nerve axotomy. We therefore explored whether a glutamate congener was toxic if applied directly within the optic nerve, or if toxicity depended upon an interaction at the cell body level. NMDA reduced retinal ganglion cell survival when applied directly into the rat optic nerve. Glutamate can be toxic if administered within the optic nerve; a direct effect at the cell body is not necessary. Future work will help to additionally unravel the steps by which axotomy induces excitotoxic damage to ganglion cells, and perhaps indicate protective interventions.
Vorwerk
C K
CK
Department of Ophthalmology, University of Pennsylvania, Scheie Eye Institute, Philadelphia, PA 19104, USA.
Naskar
R
R
Schuettauf
F
F
Zurakowski
D
D
McDermott
L M
LM
Quinto
K M
KM
Dreyer
E B
EB
D000818:Animals; D019771:Axotomy / Q000662:veterinary; D002470:Cell Survival / Q000187:drug effects; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008559:Memantine / Q000494:pharmacology; D016202:N-Methylaspartate / Q000633:toxicity*; D009409:Nerve Crush; D009900:Optic Nerve / Q000187:drug effects / Q000378:metabolism; D020221:Optic Nerve Injuries / Q000473:pathology / Q000662:veterinary*; D051381:Rats; D020318:Rats, Long-Evans; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D016202:N-Methylaspartate; D008559:Memantine