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Suppression of SNARE‐dependent exocytosis in retinal glial cells and its effect on ischemia‐induced neurodegeneration |
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| Authors: | Lysann Wagner Thomas Pannicke Vanessa Rupprecht Ina Frommherz Cornelia Volz Peter Illes Johannes Hirrlinger Herbert Jägle Veronica Egger Philip G. Haydon Frank W. Pfrieger Antje Grosche |
| Affiliation: | 1. Paul Flechsig Institute of Brain Research, University of Leipzig, Liebigstr. 19, Leipzig, 04103 Germany;2. Institute of Zoology, University of Regensburg, Universit?tsstr. 31, Regensburg, 93040 Germany;3. Department of Ophthalmology, University of Regensburg, Franz‐Josef‐Strau?‐Allee 1, Regensburg, 93953 Germany;4. Rudolf Boehm Institute for Pharmacology and Toxicology, University of Leipzig, H?rtelstr. 16/18, 04107, Leipzig, Germany;5. Carl Ludwig Institute of Physiology, University of Leipzig, Liebigstr. 27, Leipzig, 04103 Germany;6. Department of Neurogenetics, Max‐Planck‐Institute for Experimental Medicine, Hermann‐Rein‐Str. 3, G?ttingen, 37075 Germany;7. Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts, 02111 USA;8. Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5 rue Blaise Pascal, Strasbourg Cedex, 67084 France;9. Institute of Human Genetics, University of Regensburg, Franz‐Josef‐Strau?‐Allee 1, Regensburg, 93953 GermanyCorrespondence Antje Grosche, Institute of Human Genetics, University of Regensburg, Franz‐Josef‐Strau?‐Allee 11, 93053 Regensburg, Germany. Email: |
| Abstract: | Nervous tissue is characterized by a tight structural association between glial cells and neurons. It is well known that glial cells support neuronal functions, but their role under pathologic conditions is less well understood. Here, we addressed this question in vivo using an experimental model of retinal ischemia and transgenic mice for glia‐specific inhibition of soluble N‐ethylmaleimide‐sensitive factor attachment protein receptor (SNARE)‐dependent exocytosis. Transgene expression reduced glutamate, but not ATP release from single Müller cells, impaired glial volume regulation under normal conditions and reduced neuronal dysfunction and death in the inner retina during the early stages of ischemia. Our study reveals that the SNARE‐dependent exocytosis in glial cells contributes to neurotoxicity during ischemia in vivo and suggests glial exocytosis as a target for therapeutic approaches. |
| Keywords: | glutamate gliotransmitter ischemia Mü ller cell retina |