title: Characteristics of Müller glial cells in MNU-induced retinal degeneration.
abstract: Retinal Müller glial cells have been shown to undergo reactive gliosis in a variety of retinal diseases. Upregulation of glial fibrillary acidic protein (GFAP) is a hallmark of Müller cell activation. Reactive gliosis after retinal detachment or ischemia/reperfusion is characterized by hypertrophy and downregulation of inwardly rectifying K+ (Kir) currents. However, this kind of physiological alteration could not be detected in slowly progressing retinal degenerations. The photoreceptor toxin N-methyl-N-nitrosourea (MNU) leads to the rapid loss of cells in the outer nuclear layer and subsequent Müller cell activation. Here, we investigated whether Müller cells from MNU-treated mice exhibit reactive gliosis. We found that Müller cells showed increased GFAP expression and increased membrane capacitance, indicating hypertrophy. Membrane potential and Kir channel-mediated K+ currents were not significantly altered whereas Kir4.1 mRNA expression and Kir-mediated inward current densities were markedly decreased. This suggests that MNU-induced Müller cell gliosis is characterized by plasma membrane increase without alteration in the membrane content of Kir channels. Taken together, our findings show that Müller cells of MNU-treated mice are reactive and respond with a form of gliosis which is characterized by cellular hypertrophy but no changes in Kir current amplitudes.
authors.affiliation: Department of Ophthalmology,Inselspital,Bern University Hospital,University of Bern,3010 Bern,Switzerland.
authors.forename: Miriam
authors.initials: M
authors.lastname: Reisenhofer
authors.affiliation: Paul Flechsig Institute of Brain Research,Medical Faculty,University of Leipzig,04103 Leipzig,Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.affiliation: Paul Flechsig Institute of Brain Research,Medical Faculty,University of Leipzig,04103 Leipzig,Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.affiliation: Department of Ophthalmology,Inselspital,Bern University Hospital,University of Bern,3010 Bern,Switzerland.
authors.forename: Volker
authors.initials: V
authors.lastname: Enzmann
mesh_terms: D000477:Alkylating Agents / Q000633:toxicity*; D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D063928:Ependymoglial Cells / Q000378:metabolism / Q000473:pathology*; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D005911:Gliosis / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D008564:Membrane Potentials; D008770:Methylnitrosourea / Q000633:toxicity*; D051379:Mice; D008810:Mice, Inbred C57BL; D018408:Patch-Clamp Techniques; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012162:Retinal Degeneration / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D000098854:Kcnj10 Channel
chemical_list: C020932:11-cis-retinal-binding protein; D000477:Alkylating Agents; D002352:Carrier Proteins; D005904:Glial Fibrillary Acidic Protein; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; C528900:glial fibrillary astrocytic protein, mouse; D008770:Methylnitrosourea
keywords: Gliosis; Müller cells; Patch clamp; Potassium channel; Retinal degeneration