title: Deletion of aquaporin-4 renders retinal glial cells more susceptible to osmotic stress.
abstract: The glial water channel aquaporin-4 (AQP4) is implicated in the control of ion and osmohomeostasis in the sensory retina. Using retinal slices from AQP4-deficient and wild-type mice, we investigated whether AQP4 is involved in the regulation of glial cell volume under altered osmotic conditions. Superfusion of retinal slices with a hypoosmolar solution induced a rapid swelling of glial somata in tissues from AQP4 null mice but not from wild-type mice. The swelling was mediated by oxidative stress, inflammatory lipid mediators, and sodium influx into the cells and was prevented by activation of glutamatergic and purinergic receptors. Distinct inflammatory proteins, including interleukin-1 beta, interleukin-6, and inducible nitric oxide synthase, were up-regulated in the retina of AQP4 null mice compared with control, whereas cyclooxygenase-2 was down-regulated. The data suggest that water flux through AQP4 is involved in the rapid volume regulation of retinal glial (Müller) cells in response to osmotic stress and that deletion of AQP4 results in an inflammatory response of the retinal tissue. Possible implications of the data for understanding the pathophysiology of neuromyelitis optica, a human disease that has been suggested to involve serum antibodies to AQP4, are discussed.
authors.affiliation: Paul Flechsig Institute of Brain Research, University of Leipzig, Leipzig, Germany. thomas.pannicke@medizin.uni-leipzig.de
authors.forename: Thomas
authors.initials: T
authors.lastname: Pannicke
authors.forename: Antje
authors.initials: A
authors.lastname: Wurm
authors.forename: Ianors
authors.initials: I
authors.lastname: Iandiev
authors.forename: Margrit
authors.initials: M
authors.lastname: Hollborn
authors.forename: Regina
authors.initials: R
authors.lastname: Linnertz
authors.forename: Devin K
authors.initials: DK
authors.lastname: Binder
authors.forename: Leon
authors.initials: L
authors.lastname: Kohen
authors.forename: Peter
authors.initials: P
authors.lastname: Wiedemann
authors.forename: Christian
authors.initials: C
authors.lastname: Steinhäuser
authors.forename: Andreas
authors.initials: A
authors.lastname: Reichenbach
authors.forename: Andreas
authors.initials: A
authors.lastname: Bringmann
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000494:pharmacology; D000818:Animals; D051398:Aquaporin 1 / Q000235:genetics / Q000378:metabolism; D051401:Aquaporin 4 / Q000172:deficiency*; D005786:Gene Expression Regulation / Q000235:genetics; D005904:Glial Fibrillary Acidic Protein / Q000235:genetics / Q000378:metabolism; D018698:Glutamic Acid / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D009457:Neuroglia / Q000502:physiology*; D009995:Osmosis; D018384:Oxidative Stress / Q000235:genetics* / Q000502:physiology; D018408:Patch-Clamp Techniques / Q000379:methods; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012160:Retina / Q000166:cytology*; D014970:Xanthines / Q000494:pharmacology; D000098854:Kcnj10 Channel
chemical_list: C496031:Aqp4 protein, mouse; D051401:Aquaporin 4; D005904:Glial Fibrillary Acidic Protein; D007038:Hypotonic Solutions; D000098854:Kcnj10 Channel; D024661:Potassium Channels, Inwardly Rectifying; D012333:RNA, Messenger; D014970:Xanthines; D051398:Aquaporin 1; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; C051360:1,3-dipropyl-8-cyclopentylxanthine; D000241:Adenosine