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Differential susceptibility of αRGCs to glutamate excitotoxicity in autoimmune optic neuritis

Subject Area Molecular and Cellular Neurology and Neuropathology
Term from 2015 to 2023
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 262890264
 
Under autoimmune conditions, elevated neuronal calcium levels may mediate degeneration of both neuronal cell bodies and their axons, acting as a mediator of various insults and injuries involved in inflammatory attack. Identification and blockade of neuronal calcium entry pathways may therefore provide a therapeutic strategy to protect neurons from inflammationassociated death. We will explore these mechanisms in a rat model of autoimmune optic neuritis, where retinal ganglion cells undergo neurodegenerative changes beginning during the early phase of the disease. Our previous experiments have shown that calcium elevation appears to begin in the retina, where retinal ganglion cell bodies reside, before extending to the optic nerves, where their axons are located. Through a combination of in vivo (MRI, evoked potentials) and in vitro (calcium imaging, slice electrophysiology, histopathology) techniques, we will investigate calcium dynamics and calcium channel expression in these cells. Selective blocking experiments will elucidate the contribution that different calcium channels make to neurodegeneration. We will also investigate the potential of targeting these channels to achieve neuroprotection.
DFG Programme Research Units
 
 

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