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C. O. Knop, W. Behrens-Baumann, C. K. Vorwerk; Intraocular NMDA-Toxicity Can Be Reduced by Systemic MgSO4 Application in Rats. Invest. Ophthalmol. Vis. Sci. 2007;48(13):570.
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Traumatic or glaucomatous lesions of the optic nerve lead to a substantial loss of retinal ganglion cells, which are mainly due to the overstimulation of the NMDA-type of glutamate receptor of retinal ganglion cells. This results in an inadequate influx of Ca2+ Ion’s and subsequently neuronal cell death. MgSO4 has been shown to offer neuroprotective effects in cerebral ischemia and in a model of intracerebral excitotoxic insults.
Intraocular (i.o.) injections were performed with a heat-pulled glass capillary connected to a microsyringe (Drummond Microdispenser). The total volume injected per eye was 2µl. Excitotoxic lesions were induced by intravitreal injection of 20nmol NMDA. A second group of rats received in addition subcutaneous injections of MgSO4 (600mg/kg body weight in saline buffered solution) 1 hour prior to the NMDA lesion. Five days after intraocular injection, the fluorescent tracer Fluorogold was injected into the superior colliculus. Afterwards eyes were enucleated and the retina prepared as a flat-mount. Using epi-illumination, FG stained RGC’s were recorded with a digital image system, coded and analyzed in a masked fashion at 12 different areas overlaying the entire retina. All data are expressed as labeled RGC’s/mm².
Retinal ganglion cells density in controls without lesion was 1936+616 RGC/mm², whereas NMDA alone treated animals revealed a retinal ganglion cell survival of only 488+236 RGC/mm². Animals treated in addition with MgSO4 resulted in an increase of the surviving retinal ganglion cells to 869+510 RGC/mm². Controls with MgSO4 alone did not show any effect on retinal ganglion cells survival.
The endogenous blocker of the NMDA receptor associated Ca2+ channel MgSO4 can offer neuroprotective effects on retinal ganglion cells, when applicated prior to the damaging excitotoxic insult. It is encouraging, that MgSO4 might be a possible pharmacological tool to intervene in glaucomatous neuropathy, since possible imbalance of glutamate homeostasis was reported in glaucomatous eyes.
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