Expression, function and interaction of purinergic receptor subtypes on glial cells of the retina

• Applicant: Professor Dr. Andreas Reichenbach
• Subject Area: Clinical Neurology; Neurosurgery and Neuroradiology
• Term: from 2007 to 2014
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 22935240

• Final Report Year: 2015

Final Report Abstract

Within the subproject 6, we focused our research on the role of P2 receptors on retinal Müller glial cells. One of the numerous functions of these cells is the maintenance of ion and volume homeostasis in the retinal tissue. In a hypotonic solution, Müller cells could keep their volume constant. This behavior is based on a signaling cascade involving purinergic receptors. Using a variety of pharmacological tools and a number of transgenic mice, we could develop a functional scheme of this signaling cascade. We could show that Müller cells release glutamate, ATP and adenosine as gliotransmitters. We developed a method to directly detect released gliotransmitters by microfluorimetry. Whereas glutamate is released via vesicular exocytosis, ATP is set free via hemichannels. Extracellular ATP-degrading enzymes are important for the formation of ADP and adenosine. The signaling cascade and, thus, the volume homeostasis in the retina is disturbed under pathological conditions, such as in the diabetic retina or after transient retinal ischemia. However, as observed particularly in P2Y1-/- mice, the loss of functional P2 receptors may have detrimental as well as neuroprotective effects. P2 receptors are involved in some of the essential functions of glial cells within the nervous tissue. To understand the active role of glial cells in the interplay with neurons, further investigation of the role of purinergic signaling will be of eminent importance.

Publications

• Altered immune response in mice deficient for the G protein-coupled receptor GPR 34. J Biol Chem. 2010; 286: 2101–10
  Liebscher I, Müller U, Teupser D, Engemaier E, Engel KMJ, Ritscher L, Thor D, Sangkuhl K, Ricken A, Wurm A, Piehler D, Schmutzler S, Fuhrmann H, Albert FW, Reichenbach A, Thiery J, Schöneberg T, Schulz A
  
• Endogenous purinergic signaling is required for osmotic volume regulation of retinal glial cells. J Neurochem. 2010; 112: 1261–72
  Wurm A, Lipp S, Pannicke T, Linnertz R, Krügel U, Schulz A, Färber K, Zahn D, Grosse J, Wiedemann P, Chen J, Schöneberg T, Illes P, Reichenbach A, Bringmann A
  
• Erythropoietin inhibits osmotic swelling of retinal glial cells by Janus kinase- and extracellular signal-regulated kinases1/2-mediated release of vascular endothelial growth factor. Neuroscience. 2010; 165: 1147–58
  Krügel K, Wurm A, Linnertz R, Pannicke T, Wiedemann P, Reichenbach A, Bringmann A
  
• Effects of ischemia-reperfusion on physiological properties of Müller glial cells in the porcine retina. Invest Ophthalmol Vis Sci. 2011; 52: 3360–7
  Wurm A, Iandiev I, Uhlmann S, Wiedemann P, Reichenbach A, Bringmann A, Pannicke T
  
• Involvement of oxidative stress and mitochondrial dysfunction in the osmotic swelling of retinal glial cells from diabetic rats. Exp Eye Res. 2011; 92: 87–93
  Krügel K, Wurm A, Pannicke T, Hollborn M, Karl A, Wiedemann P, Reichenbach A, Kohen L, Bringmann A
  
• Purinergic signaling involved in Müller cell function in the mammalian retina. Prog Retin Eye Res. 2011; 30: 324–42
  Wurm A, Pannicke T, Iandiev I, Francke M, Hollborn M, Wiedemann P, Reichenbach A, Osborne NN, Bringmann A
  
• Synergistic action of hypoosmolarity and glutamine in inducing acute swelling of retinal glial (Müller) cells. Glia. 2011; 59: 256–66
  Karl A, Wurm A, Pannicke T, Krügel K, Obara-Michlewska M, Wiedemann P, Reichenbach A, Albrecht J, Bringmann A
  
• Mechanisms of VEGF- and glutamate-induced inhibition of osmotic swelling of murine retinal glial (Müller) cells: Indications for the involvement of vesicular glutamate release and connexinmediated ATP release. Neurochem Res. 2012; 37: 268–78
  Brückner E, Grosche A, Pannicke T, Wiedemann P, Reichenbach A, Bringmann A
  
• Physiologic properties of Müller cells from human eyes affected with melanoma. Invest Ophthalmol Vis Sci. 2012; 53: 4170–6
  Grosche A, Pannicke A, Karl A, Iandiev I, Francke M, Wiedemann P, Reichenbach A, Bringmann A
  
• Relevance of exocytotic glutamate release from retinal glia. Neuron. 2012; 74: 405–16
  Slezak M, Grosche A, Niemiec A, Tanimoto N, Pannicke T, Münch TA, Crocker B, Isope P, Härtig W, Beck SC, Huber G, Ferracci G, Perraut M, Reber M, Miehe M, Demais V, Lévêque C, Metzger D, Szklarczyk K, Przewlocki R, Seeliger M, Sage-Ciocca D, Hirrlinger J, Reichenbach A, Reibel S, Pfrieger FW
  
• Ca2+ microfluorimetry in retinal Müller glial cells. Methods Mol Biol. 2013; 935: 257–70
  Wurm A, Pannicke T, Reichenbach A
  
• Hypoosmotic and glutamate-induced swelling of bipolar cells in the rat retina: comparison with swelling of Müller glial cells. J Neurochem. 2013; 126: 372–81
  Vogler S, Grosche A, Pannicke T, Ulbricht E, Wiedemann P, Reichenbach A, Bringmann A
  
• Neuroscience. Developmental refining of neuroglial signaling? Science. 2013; 339: 152–3
  Grosche A, Reichenbach A
  
• Osteopontin inhibits osmotic swelling of retinal glial (Müller) cells by inducing release of VEGF. Neuroscience. 2013; 246: 59–72
  Wahl V, Vogler S, Grosche A, Pannicke T, Ueffing M, Wiedemann P, Reichenbach A, Hauck SM, Bringmann A
  
• Differential effects of P2Y1 deletion on glial activation and survival of photoreceptors and amacrine cells in the ischemic mouse retina. Cell Death Dis. 2014; 5: e1353
  Pannicke T, Frommherz I, Biedermann B, Wagner L, Sauer K, Ulbricht E, Härtig W, Krügel U, Ueberham U, Arendt T, Illes P, Bringmann A, Reichenbach A, Grosche A
  
• Purinergic neuron-glia interactions in sensory systems. Pflugers Arch. 2014; 466: 1859–72
  Lohr C, Grosche A, Reichenbach A, Hirnet D
  
• Altered microglial phagocytosis in GPR34-deficient mice. Glia. 2015; 63: 206–15
  Preissler J, Grosche A, Lede V, Le Duc D, Krügel K, Matyash V, Szulzewsky F, Kallendrusch S, Immig K, Kettenmann H, Bechmann I, Schöneberg T, Schulz A