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MgSO4 is Neuroprotective in a Model of Intravitreal Excitotoxicity

1Knop C., 1Banaskiewicz R., 2Behrens-Baumann W., 1Vorwerk C. K.,
1Otto-von-Guericke-Universität Magdeburg, Klinik und Poliklinik für Augenheilkunde, Forschungslabor II (Magdeburg)
2Otto-von-Guericke-Universität Magdeburg, Universitäts-Augenklinik (Magdeburg)

Introduction: 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. In this study we investigated, if MgSO4, an endogenous blocker of the NMDA receptor associated Ion channel, can offer neuroprotective effects in a model of acute excitotoxic stimulation of retinal ganglion cells. MgSO4, has been shown to offer neuroprotective effects in cerebral ischemia and in a model of intracerebral excitotoxic insults.
Material & Methods: In one group of rats, excitotoxic lesions were induced by intraocular (i.o.) injection of 20nmol NMDA. A second group received in addition subcutaneous injections of MgSO4 (120mg/kg body weight in saline buffered solution) 1,3 and 5 days prior to the i.o. NMDA lesion. 5 days after the excitotoxic retinal damage, retinal ganglion cells were labeled with fluorogold. After additional 4 day eyes were enucleated and retinal whole mounts counted for fluorogold positive retinal ganglion cells in a masked fashion at 12 different areas overlaying the entire retina.
Results: Retinal ganglion cells density in controls without lesion was 2273+148 RGC/mm2, whereas NMDA alone treated animals revealed a retinal ganglion cell survival of only 349+38 RGC/mm2. Animals treated in addition with MgSO4 resulted in a increase of the surviving retinal ganglion cells to 595+108 RGC/mm2. Controls with MgSO4 alone did not show any effect on retinal ganglion cells survival.
Conclusions: 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. Although these are preliminary results, it is encouraging, that MgSO4 might be also able to be a possible pharmacological tool to intervene with previous reported elevated levels of glutamate in glaucomatous eyes.