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Journal of neuroinflammation2016; 13(1); 89; doi: 10.1186/s12974-016-0554-2

Aquaporin 11, a regulator of water efflux at retinal Müller glial cell surface decreases concomitant with immune-mediated gliosis.

Abstract: Müller glial cells are important regulators of physiological function of retina. In a model disease of retinal inflammation and spontaneous recurrent uveitis in horses (ERU), we could show that retinal Müller glial cells significantly change potassium and water channel protein expression during autoimmune pathogenesis. The most significantly changed channel protein in neuroinflammatory ERU was aquaporin 11 (AQP11). Aquaporins (AQP, 13 members) are important regulators of water and small solute transport through membranes. AQP11 is an unorthodox member of this family and was assigned to a third group of AQPs because of its difference in amino acid sequence (conserved sequence is only 11 %) and especially its largely unknown function. Methods: In order to gain insight into the distribution, localization, and function of AQP11 in the retina, we first developed a novel monoclonal antibody for AQP11 enabling quantification, localization, and functional studies. Results: In the horse retina, AQP11 was exclusively expressed at Müller glial cell membranes. In uveitic condition, AQP11 disappeared from gliotic Müller cells concomitant with glutamine synthase. Since function of AQP11 is still under debate, we assessed the impact of AQP11 channel on cell volume regulation of primary Müller glial cells under different osmotic conditions. We conclude a concomitant role for AQP11 with AQP4 in water efflux from these glial cells, which is disturbed in ERU. This could probably contribute to swelling and subsequent severe complication of retinal edema through impaired intracellular fluid regulation. Conclusions: Therefore, AQP11 is important for physiological Müller glia function and the expression pattern and function of this water channel seems to have distinct functions in central nervous system. The significant reduction in neuroinflammation points to a crucial role in pathogenesis of autoimmune uveitis.
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Publication Date: 2016-04-23 PubMed ID: 27107718PubMed Central: PMC4842293DOI: 10.1186/s12974-016-0554-2Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the role of a protein called Aquaporin 11 (AQP11) in regulating water and potassium channels in retinal Müller glial cells, especially during retinal inflammation and spontaneous recurrent uveitis in horses. It finds that changes in AQP11 protein expression could contribute to retinal swelling and complications of retinal edema by impairing regulation of intracellular fluid.

Background

  • Müller glial cells play a crucial role in the physiological function of the retina. In horses with Equine Recurrent Uveitis (ERU), an autoimmune disease associated with retinal inflammation, researchers observed that these cells underwent significant changes in potassium and water channel protein expression.
  • The channel protein that underwent the most significant changes was AQP11, a part of the Aquaporins family responsible for regulating water and small solute transport through cellular membranes. AQP11 is unique within this family due to differences in its amino acid sequence and its largely unknown function.

Research Methodology

  • To gain a better understanding of AQP11’s distribution, location, and function in the retina, researchers first developed a new monoclonal antibody to enable quantification, localization, and functional studies of AQP11.

Results

  • In the retinas of horses, AQP11 was found solely on Müller glial cell membranes.
  • Under uveitic conditions (inflammation), AQP11 and an enzyme called glutamine synthase both disappeared from gliotic Müller cells.
  • The researchers studied the effect of AQP11 on cell volume regulation in primary Müller glial cells under differing osmotic conditions. Their findings suggest that AQP11 works in conjunction with another protein, AQP4, in facilitating water efflux from these cells, a process that becomes disrupted in ERU.
  • This disruption could contribute to the onset of retinal swelling and serious complications of retinal edema by impairing the regulation of intracellular fluid.

Conclusions

  • AQP11 is integral to the physiological function of Müller glia. The specific expression pattern and functionality of this water channel seem to have unique roles within the central nervous system.
  • The considerable reduction of AQP11 during neuroinflammation indicates a critical role in the pathogenesis of autoimmune uveitis.

Cite This Article

APA
Deeg CA, Amann B, Lutz K, Hirmer S, Lutterberg K, Kremmer E, Hauck SM. (2016). Aquaporin 11, a regulator of water efflux at retinal Müller glial cell surface decreases concomitant with immune-mediated gliosis. J Neuroinflammation, 13(1), 89. https://doi.org/10.1186/s12974-016-0554-2

Publication

Journal of neuroinflammation
ISSN: 1742-2094
NlmUniqueID: 101222974
Country: England
Language: English
Volume: 13
Issue: 1
Pages: 89

Researcher Affiliations

Deeg, Cornelia A
  • Experimental Ophthalmology, Philipps University of Marburg, Baldingerstrasse, 35033, Marburg, Germany. Cornelia.Deeg@uni-marburg.de.
  • Department of Veterinary Sciences, Institute of Animal Physiology, Ludwig-Maximilians University, Veterinärstr. 13, 80539, München, Germany. Cornelia.Deeg@uni-marburg.de.
Amann, Barbara
  • Department of Veterinary Sciences, Institute of Animal Physiology, Ludwig-Maximilians University, Veterinärstr. 13, 80539, München, Germany.
Lutz, Konstantin
  • Department of Veterinary Sciences, Institute of Animal Physiology, Ludwig-Maximilians University, Veterinärstr. 13, 80539, München, Germany.
Hirmer, Sieglinde
  • Department of Veterinary Sciences, Institute of Animal Physiology, Ludwig-Maximilians University, Veterinärstr. 13, 80539, München, Germany.
Lutterberg, Karina
  • Department of Veterinary Sciences, Institute of Animal Physiology, Ludwig-Maximilians University, Veterinärstr. 13, 80539, München, Germany.
Kremmer, Elisabeth
  • Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), Institute for Molecular Immunology, Marchioninistraße 25, 81377, München, Germany.
Hauck, Stefanie M
  • Department of Protein Science, Helmholtz Zentrum München-German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, 85764, Neuherberg, Germany.

MeSH Terms

  • Animals
  • Aquaporins / immunology
  • Aquaporins / metabolism
  • Autoimmune Diseases / metabolism
  • Autoimmune Diseases / pathology
  • Autoimmune Diseases / veterinary
  • Blotting, Western
  • Ependymoglial Cells / metabolism
  • Gliosis / immunology
  • Gliosis / metabolism
  • Gliosis / veterinary
  • Horse Diseases
  • Horses
  • Immunohistochemistry
  • Osmotic Pressure
  • Uveitis / metabolism
  • Uveitis / pathology
  • Uveitis / veterinary

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This article has been cited 11 times.
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