Retinal ganglion cells from mice deficient in neuronal nitric oxide synthase exhibit normal calcium fluxes in response to glutamate

Q. D. Nguyen, C. K. Vorwerk, E. B. Dreyer

Research output: Contribution to journalArticle

Abstract

Purpose. Neuronal nitric oxide synthase (nNOS) plays a critical role in many neuronal processes, and is necessary for the full expression of excitotoxic damage. Huang et al have engineered mice deficient in neuronal nitric oxide synthase. (Cell, 75:1273-86, 1993). Glutamate-mediated (through the N-methyl-D aspartate, NMDA) receptor excitotoxicity can cause selective damage to retinal ganglion cells both in vitro and in vivo. We have shown that after an NMDA intraocular injection, nNOS knockout (nNOS-) mice lost only half as many retinal ganglion cells as littermate controls, indicating that nNOS is a prerequisite for the full expression of NMDA retinal excitotoxicity. NMDA leads to a pronounced rise in intracellular calcium, which can activate several enzymes including the calmodulin-dependent NOS, implicated in cell death. We therefore sought to establish whether nNOS- mice had a normal intracellular response to NMDA/glutamate. Methods. Varying concentrations of NMDA and glutamate were added to retinal ganglion cells. Concentrations of calcium were monitored through fura 2 imaging, both in nNOS- mice and in control littermates. Results. Retinal ganglion cells from nNOS- mice show similar elevations in calcium post-NMDA stimulation compared to those from littermate controls. Conclusions. The relative resistance of nNOS- mice to excitotoxic damage is independent of any perturbation in the initial cellular response to NMDA, and is a consequence of downstream effects.

Original languageEnglish (US)
Pages (from-to)S627
JournalInvestigative Ophthalmology and Visual Science
Volume37
Issue number3
StatePublished - Feb 15 1996

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Nitric Oxide Synthase Type I
Retinal Ganglion Cells
N-Methylaspartate
Glutamic Acid
Calcium
Intraocular Injections
Fura-2
Calmodulin
N-Methyl-D-Aspartate Receptors
Knockout Mice
Cell Death
Enzymes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

Retinal ganglion cells from mice deficient in neuronal nitric oxide synthase exhibit normal calcium fluxes in response to glutamate. / Nguyen, Q. D.; Vorwerk, C. K.; Dreyer, E. B.

In: Investigative Ophthalmology and Visual Science, Vol. 37, No. 3, 15.02.1996, p. S627.

Research output: Contribution to journalArticle

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