title: Suppression of SNARE-dependent exocytosis in retinal glial cells and its effect on ischemia-induced neurodegeneration.
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.
authors.affiliation: Paul Flechsig Institute of Brain Research, University of Leipzig, Liebigstr. 19, Leipzig, 04103, Germany.
authors.forename: Lysann
authors.initials: L
authors.lastname: Wagner
authors.affiliation: Paul Flechsig Institute of Brain Research, University of Leipzig, Liebigstr. 19, Leipzig, 04103, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.affiliation: Institute of Zoology, University of Regensburg, Universitätsstr. 31, Regensburg, 93040, Germany.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Rupprecht
authors.affiliation: Paul Flechsig Institute of Brain Research, University of Leipzig, Liebigstr. 19, Leipzig, 04103, Germany.
authors.forename: Ina
authors.initials: I
authors.lastname: Frommherz
authors.affiliation: Department of Ophthalmology, University of Regensburg, Franz-Josef-Strauß-Allee 1, Regensburg, 93953, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Volz
authors.affiliation: Rudolf Boehm Institute for Pharmacology and Toxicology, University of Leipzig, Härtelstr. 16/18, 04107, Leipzig, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Illes
authors.affiliation: Carl Ludwig Institute of Physiology, University of Leipzig, Liebigstr. 27, Leipzig, 04103, Germany.|Department of Neurogenetics, Max-Planck-Institute for Experimental Medicine, Hermann-Rein-Str. 3, Göttingen, 37075, Germany.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hirrlinger
authors.affiliation: Department of Ophthalmology, University of Regensburg, Franz-Josef-Strauß-Allee 1, Regensburg, 93953, Germany.
authors.forename: Herbert
authors.initials: H
authors.lastname: Jägle
authors.affiliation: Institute of Zoology, University of Regensburg, Universitätsstr. 31, Regensburg, 93040, Germany.
authors.forename: Veronica
authors.initials: V
authors.lastname: Egger
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, 136 Harrison Avenue, Boston, Massachusetts, 02111, USA.
authors.forename: Philip G
authors.initials: PG
authors.lastname: Haydon
authors.affiliation: Institute of Cellular and Integrative Neurosciences, CNRS UPR 3212, University of Strasbourg, 5 rue Blaise Pascal, Strasbourg Cedex, 67084, France.
authors.forename: Frank W
authors.initials: FW
authors.lastname: Pfrieger
authors.affiliation: Institute of Human Genetics, University of Regensburg, Franz-Josef-Strauß-Allee 1, Regensburg, 93953, Germany.
authors.forename: Antje
authors.identifier: 0000-0003-0338-7530
authors.initials: A
authors.lastname: Grosche
mesh_terms: D000818:Animals; D002135:Calcium-Binding Proteins / Q000378:metabolism; D004195:Disease Models, Animal; D004318:Doxycycline / Q000627:therapeutic use; D063928:Ependymoglial Cells / Q000378:metabolism; D005089:Exocytosis / Q000235:genetics*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D007382:Intermediate Filaments / Q000378:metabolism; D007511:Ischemia / Q000150:complications* / Q000473:pathology; D008027:Light; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins / Q000378:metabolism; D009410:Nerve Degeneration / Q000209:etiology*; D051571:Protein Kinase C-alpha / Q000378:metabolism; D058472:Receptors, Purinergic P2Y1 / Q000172:deficiency / Q000235:genetics; D012160:Retina / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000378:metabolism*; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D005904:Glial Fibrillary Acidic Protein; D008840:Microfilament Proteins; D058472:Receptors, Purinergic P2Y1; D050600:SNARE Proteins; D042461:Vascular Endothelial Growth Factor A; D018698:Glutamic Acid; D051571:Protein Kinase C-alpha; D004318:Doxycycline
keywords: Müller cell; gliotransmitter; glutamate; ischemia; retina