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Glia2011; 59(5); 697-707; doi: 10.1002/glia.21139

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.
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Publication Date: 2011-02-08 PubMed ID: 21305615DOI: 10.1002/glia.21139Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

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This study examined the role of retinal Müller glial cells, in particular their ion and water balance, in horses with equine recurrent uveitis (ERU). The research found significant changes in membrane proteins related to these functions, indicating a potential imbalance in the cells’ response to this autoimmune condition.

Overview of the Study

  • This research was focused on autoimmune uveitis, a severe eye disease that threatens vision and is characterized by recurrent flare-ups caused by autoaggressive T-cells. The study specifically examined equine recurrent uveitis (ERU), a spontaneous disease in horses that mirrors the human version.
  • The primary objective was to understand the function of retinal Müller glial cells in ERU. These cells play a vital role in maintaining the retina, and the researchers investigated how certain membrane proteins engaged in ion and water balance operate within these cells.

Findings

  • The study identified that the channel Kir2.1 was highly expressed in diseased retinas, whereas the expression of Kir4.1 was reduced compared to control subjects. The increased expression of Kir2.1 was associated with Müller cells in the control subjects, but this pattern changed in the uveitis-affected retinas.
  • Another crucial finding was the significant increase in the expression of the water-channel protein AQP4 in the affected retinas. There was also a noticeable shift in this protein’s distribution from Müller cells in healthy subjects to a circular expression pattern in the ERU subjects’ outer nuclear layer.
  • The study also discovered the presence of the aquaporin family protein AQP5 in Müller cells, largely concentrated in the cells’ secondary processes. AQP5 was round to be significantly decreased in uveitis.

Conclusions

  • The study confirmed that in autoimmune uveitis, retinal Müller glial cells undergo substantial changes in their water and ion physiology. This finding suggests an imbalance in these cells’ response to the autoimmune condition, an insight that could help inform future studies and potential treatments.

Cite This Article

APA
Eberhardt C, Amann B, Feuchtinger A, Hauck SM, Deeg CA. (2011). 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. Glia, 59(5), 697-707. https://doi.org/10.1002/glia.21139

Publication

Glia
ISSN: 1098-1136
NlmUniqueID: 8806785
Country: United States
Language: English
Volume: 59
Issue: 5
Pages: 697-707

Researcher Affiliations

Eberhardt, Christina
  • Department of Veterinary Sciences, Institute of Animal Physiology, Ludwig-Maximilians University, München, Germany.
Amann, Barbara
    Feuchtinger, Annette
      Hauck, Stefanie M
        Deeg, Cornelia A

          MeSH Terms

          • Animals
          • Aquaporin 4 / metabolism
          • Aquaporin 5 / metabolism
          • Autoimmune Diseases / metabolism
          • Autoimmune Diseases / physiopathology
          • Blotting, Western
          • Horses
          • Immunohistochemistry
          • Neuroglia / metabolism
          • Neurons / metabolism
          • Potassium Channels, Inwardly Rectifying / metabolism
          • Retina / cytology
          • Retina / metabolism
          • Statistics, Nonparametric
          • Uveitis / metabolism
          • Uveitis / physiopathology
          • Water-Electrolyte Balance / physiology

          Citations

          This article has been cited 22 times.
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