N‐methyl‐D‐aspartate‐mediated glutamate toxicity in the developing rabbit retina

N‐methyl‐D‐aspartate‐mediated glutamate toxicity in the developing rabbit retina Extracellular levels of endogenous glutamate are relatively high in the developing rabbit retina but nonetheless appear to promote cell survival and developmental processes at concentrations considered toxic in the adult. We wished to examine the development of retinal susceptibility to glutamate toxicity as well as the protective effects of two N‐methyl‐D‐aspartate (NMDA) antagonists, 2‐amino‐5‐phosphono‐5‐valeric acid (APV) and dextromethorphan (Dex), and the nitric oxide synthase (NOS) inhibitor, NG‐methyl‐L‐arginine (metARG). One day in vitro retinal explants of adult and neonatal rabbits were incubated with various agonists and antagonists, and stained with trypan blue to visualize necrotic cells. The density of the necrotic cells was analyzed using the Zeiss Videoplan 2. Immature neurons were approximately 10‐fold less sensitive to NMDA toxicity compared to the adult. Although both NMDA antagonists and met ARG provided marked protection for adult retinal neurons against glutamate toxicity, the modest susceptibility of the immature neuron was blocked only by Dex and not APV or metARG. At least two factors may contribute to the ability or the neonatal retina to survive in the presence of high levels of endogenous extracellular glutamate. First, the 10‐fold developmental increase in NMDA toxicity occurs simultaneously with a 12–15‐fold downregulation of extracellular glutamate, probably through the actions of maturing Muller cells. Second, the NMDA/NO excitotoxic pathway may not be active at birth since an NOS inhibitor had little effect at this stage and our previous morphological data demonstrate that NOS‐containing cells are not present in their mature configuration until the second postnatal week. J. Neurosci. Res. 47:416–426, 1997. © 1997 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Journal of Neuroscience Research Wiley

N‐methyl‐D‐aspartate‐mediated glutamate toxicity in the developing rabbit retina

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Publisher
Wiley
Copyright
Copyright © 1997 Wiley‐Liss, Inc.
ISSN
0360-4012
eISSN
1097-4547
D.O.I.
10.1002/(SICI)1097-4547(19970215)47:4<416::AID-JNR7>3.0.CO;2-H
Publisher site
See Article on Publisher Site

Abstract

Extracellular levels of endogenous glutamate are relatively high in the developing rabbit retina but nonetheless appear to promote cell survival and developmental processes at concentrations considered toxic in the adult. We wished to examine the development of retinal susceptibility to glutamate toxicity as well as the protective effects of two N‐methyl‐D‐aspartate (NMDA) antagonists, 2‐amino‐5‐phosphono‐5‐valeric acid (APV) and dextromethorphan (Dex), and the nitric oxide synthase (NOS) inhibitor, NG‐methyl‐L‐arginine (metARG). One day in vitro retinal explants of adult and neonatal rabbits were incubated with various agonists and antagonists, and stained with trypan blue to visualize necrotic cells. The density of the necrotic cells was analyzed using the Zeiss Videoplan 2. Immature neurons were approximately 10‐fold less sensitive to NMDA toxicity compared to the adult. Although both NMDA antagonists and met ARG provided marked protection for adult retinal neurons against glutamate toxicity, the modest susceptibility of the immature neuron was blocked only by Dex and not APV or metARG. At least two factors may contribute to the ability or the neonatal retina to survive in the presence of high levels of endogenous extracellular glutamate. First, the 10‐fold developmental increase in NMDA toxicity occurs simultaneously with a 12–15‐fold downregulation of extracellular glutamate, probably through the actions of maturing Muller cells. Second, the NMDA/NO excitotoxic pathway may not be active at birth since an NOS inhibitor had little effect at this stage and our previous morphological data demonstrate that NOS‐containing cells are not present in their mature configuration until the second postnatal week. J. Neurosci. Res. 47:416–426, 1997. © 1997 Wiley‐Liss, Inc.

Journal

Journal of Neuroscience ResearchWiley

Published: Feb 15, 1997

References

  • Nitric oxide, a novel neuronal messenger
    Bredt, Bredt; Snyder, Snyder
  • Nitric oxide‐mediated death of cultured neonatal retinal ganglion cells: Neuroprotective properties of glutamate and chondroitin sulfate proteoglycan
    Nichol, Nichol; Schulz, Schulz; Bennett, Bennett
  • Excitotoxicity and the NMDA receptor
    Rothman, Rothman; Olney, Olney

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