title: Differential expression of inwardly rectifying K+ channels and aquaporins 4 and 5 in autoimmune uveitis indicates misbalance in Müller glial cell-dependent ion and water homeostasis.
abstract: Reactive gliosis is a well-established response to virtually every retinal disease. Autoimmune uveitis, a sight threatening disease, is characterized by recurrent relapses through autoaggressive T-cells. The purpose of this study was to assess retinal Müller glial cell function in equine recurrent uveitis (ERU), a spontaneous disease model resembling the human disease, by investigating membrane proteins implicated in ion and water homeostasis. We found that Kir2.1 was highly expressed in diseased retinas, whereas Kir4.1 was downregulated in comparison to controls. Distribution of Kir2.1 appeared Müller cell associated in controls, whereas staining of cell somata in the inner nuclear layer was observed in uveitis. In contrast to other subunits, Kir4.1 was evenly expressed along equine Müller cells, whereas in ERU, Kir4.1 almost disappeared from Müller cells. Hence, we suggest a different mechanism for potassium buffering in the avascular equine retina and, moreover, an impairment in uveitis. Uveitic retinas showed significantly increased expression of AQP4 as well as a displaced expression from Müller cells in healthy specimens to an intense circular expression pattern in the outer nuclear layer in ERU cases. Most interestingly, we detected the aquaporin family member protein AQP5 to be expressed in Müller cells with strong enrichments in Müller cell secondary processes. This finding indicates that fluid regulation within the equine retina may be achieved by an additional aquaporin. Furthermore, AQP5 was significantly decreased in uveitis. We conclude that the Müller cell response in autoimmune uveitis implies considerable changes in its potassium and water physiology.
authors.affiliation: Department of Veterinary Sciences, Institute of Animal Physiology, Ludwig-Maximilians University, München, Germany.
authors.forename: Christina
authors.initials: C
authors.lastname: Eberhardt
authors.forename: Barbara
authors.initials: B
authors.lastname: Amann
authors.forename: Annette
authors.initials: A
authors.lastname: Feuchtinger
authors.forename: Stefanie M
authors.initials: SM
authors.lastname: Hauck
authors.forename: Cornelia A
authors.initials: CA
authors.lastname: Deeg
mesh_terms: D000818:Animals; D051401:Aquaporin 4 / Q000378:metabolism*; D051402:Aquaporin 5 / Q000378:metabolism*; D001327:Autoimmune Diseases / Q000378:metabolism* / Q000503:physiopathology; D015153:Blotting, Western; D006736:Horses; D007150:Immunohistochemistry; D009457:Neuroglia / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000378:metabolism*; D012160:Retina / Q000166:cytology / Q000378:metabolism*; D018709:Statistics, Nonparametric; D014605:Uveitis / Q000378:metabolism* / Q000503:physiopathology; D014882:Water-Electrolyte Balance / Q000502:physiology*
chemical_list: D051401:Aquaporin 4; D051402:Aquaporin 5; D024661:Potassium Channels, Inwardly Rectifying