title: Upregulation of extracellular ATP-induced Müller cell responses in a dispase model of proliferative vitreoretinopathy.
abstract: OBJECTIVE
  To test whether in an animal model of proliferative vitreoretinopathy (PVR) the Müller glial cells displayed an upregulation of purinergic P2 receptor-mediated responses.
  
  
  METHODS
  PVR was induced by intravitreal injection of the proteolytic enzyme, dispase, in the eyes of adult rabbits. The developing PVR was examined ophthalmoscopically. After 3 weeks, small retinal pieces were wholemounted and used for calcium imaging, freshly dissociated Müller cells were subjected to calcium imaging, and patch-clamp recordings were made. The presence of P2 receptor-mediated Ca(2+) responses was determined both directly--that is, fluorometrically--and indirectly, by electrophysiological recording of Ca(2+)-activated K(+) currents.
  
  
  RESULTS
  According to earlier observations in another model of retinal detachment and PVR, the reactive Müller cells displayed hypertrophy, downregulation of inwardly rectifying K(+) currents, and depolarization of the resting membrane potential, all dependent on the severity of the PVR. Further, significant PVR-induced increase was observed in the number of Müller cells responding to adenosine 5'-triphosphate (ATP), with a transient elevation of their [Ca(2+)](i). If isolated Müller cells were exposed to ATP, 13% of the control cells, but 29% (moderate PVR) or 53% (massive PVR) of the reactive cells, showed fluorometric Ca(2+) increases. An increase of Ca(2+)-activated K(+) currents was measured in 11% of the control cells, but in 83% (moderate PVR) and 90% (massive PVR) of the reactive cells. Confocal images of retinal wholemounts revealed similar results. Because similar responses were elicited by uridine triphosphate (UTP), the dominant involvement of metabotropic (P2Y type) purinergic receptors is suggested.
  
  
  CONCLUSIONS
  An upregulation of purinergic receptors is part of the reactive changes of Müller cells during PVR. It is suggested that ATP-evoked Ca(2+) responses may support the proliferation of Müller cells during PVR.
authors.affiliation: Department of Neurophysiology, Paul Flechsig Institute for Brain Research, University of Leipzig, Jahnallee 59, D-04109 Leipzig, Germany. fram@medizin.uni-leipzig.de
authors.forename: Mike
authors.initials: M
authors.lastname: Francke
authors.forename: Michael
authors.initials: M
authors.lastname: Weick
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.forename: Ortrud
authors.initials: O
authors.lastname: Uckermann
authors.forename: Jens
authors.initials: J
authors.lastname: Grosche
authors.forename: Iwona
authors.initials: I
authors.lastname: Goczalik
authors.forename: Ivan
authors.initials: I
authors.lastname: Milenkovic
authors.forename: Susanne
authors.initials: S
authors.lastname: Uhlmann
authors.forename: Frank
authors.initials: F
authors.lastname: Faude
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
mesh_terms: D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000814:Aniline Compounds / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D010450:Endopeptidases; D005260:Female; D006984:Hypertrophy; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D008564:Membrane Potentials; D018613:Microscopy, Confocal; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D018408:Patch-Clamp Techniques; D024681:Potassium Channels, Calcium-Activated / Q000378:metabolism; D011817:Rabbits; D018048:Receptors, Purinergic P2 / Q000378:metabolism*; D015854:Up-Regulation; D018630:Vitreoretinopathy, Proliferative / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D014966:Xanthenes / Q000378:metabolism
chemical_list: D000814:Aniline Compounds; C409648:Fluo 4; D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D018048:Receptors, Purinergic P2; D014966:Xanthenes; D000255:Adenosine Triphosphate; D010450:Endopeptidases; C023139:dispase; D002118:Calcium