Suppression of SNARE‐dependent exocytosis in retinal glial cells and its effect on ischemia‐induced neurodegeneration

• Published in: Glia 2017-07, Vol.65 (7), p.1059-1071
• Main Authors: Wagner, Lysann, Pannicke, Thomas, Rupprecht, Vanessa, Frommherz, Ina, Volz, Cornelia, Illes, Peter, Hirrlinger, Johannes, Jägle, Herbert, Egger, Veronica, Haydon, Philip G., Pfrieger, Frank W., Grosche, Antje
• Format: Article
• Language: English
• Subjects: Animals; Calcium-Binding Proteins - metabolism; Disease Models, Animal; Doxycycline - therapeutic use; Ependymoglial Cells - metabolism; Exocytosis; Exocytosis - genetics; Glial cells; Glial Fibrillary Acidic Protein - genetics; Glial Fibrillary Acidic Protein - metabolism; gliotransmitter; glutamate; Glutamic Acid - metabolism; Human health and pathology; Intermediate Filaments - metabolism; Ischemia; Ischemia - complications; Ischemia - pathology; Life Sciences; Light; Mice; Mice, Transgenic; Microfilament Proteins - metabolism; Müller cell; N-Ethylmaleimide-sensitive protein; Nerve Degeneration - etiology; Neurodegeneration; Neuronal-glial interactions; Neurotoxicity; Protein Kinase C-alpha - metabolism; Receptors, Purinergic P2Y1 - deficiency; Receptors, Purinergic P2Y1 - genetics; Retina; Retina - pathology; Retinal Ganglion Cells - metabolism; Rodents; SNAP receptors; SNARE Proteins - genetics; SNARE Proteins - metabolism; Transgenic mice; Vascular Endothelial Growth Factor A - metabolism
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.23144

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. Main Points SNARE‐dependent exocytosis was observed in retinal Müller glial cells. Glutamate is released by exocytosis whereas ATP release is likely to be non‐vesicular. Suppression of SNARE‐dependent exocytosis in glial cells has a neuroprotective effect.