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 language||English (US)|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Feb 15 1996|
ASJC Scopus subject areas
- Sensory Systems
- Cellular and Molecular Neuroscience