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Mike Francke, Michael Weick, Thomas Pannicke, Ortrud Uckermann, Jens Grosche, Iwona Goczalik, Ivan Milenkovic, Susanne Uhlmann, Frank Faude, Peter Wiedemann, Andreas Reichenbach, Andreas Bringmann; Upregulation of Extracellular ATP-Induced Müller Cell Responses in a Dispase Model of Proliferative Vitreoretinopathy. Invest. Ophthalmol. Vis. Sci. 2002;43(3):870-881.
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© ARVO (1962-2015); The Authors (2016-present)
purpose. 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
Ca2+ responses was determined both directly—that is,
fluorometrically, and indirectly, by electrophysiological recording of
Ca2+-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[
Ca2+]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
Ca2+ increases. An increase of Ca2+-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
Ca2+ responses may support the proliferation of
Müller cells during PVR.
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