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C. Eberhardt, B. Amann, S. M. Hauck, C. A. Deeg; Changes in Mueller Glial Cell Membrane Channels in Spontaneous Recurrent Uveitis. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5754.
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© ARVO (1962-2015); The Authors (2016-present)
Equine recurrent uveitis (ERU) is a spontaneous disease with high prevalence in horses, leading to blindness. It is the only spontaneous animal model for human autoimmune uveitis. Ongoing inflammation in course of disease leads to changes in morphology of Mueller glial cells. To further investigate the role of Mueller cells in ERU pathogenesis we studied expression patterns of different membrane channels such as potassium- and aquaporin channels.
Immunohistochemistry was performed on paraffin embedded eye sections to investigate expression patterns of potassium channel Kir 4.1 and water channel Aquaporin 4 (AQP4) in comparison to the specific Mueller cell intermediate filaments glial fibrillary acidic protein (GFAP), Vimentin and Glutamine Synthetase (GS) in horses with ERU and negative controls. We used monoclonal goat antibody specific for Kir 4.1 (Santa Cruz) and monoclonal mouse antibody specific for AQP4 (Santa Cruz) for candidate detection in tissue. Rabbit-anti-GFAP antibody (Dako Cytomation), mouse-anti-Vimentin antibody (Sigma Aldrich) and mouse-anti-GS antibody (BD Biosciences) served as Mueller cell specific markers. Candidate expression was further quantified using Western Blot analysis.
Mueller cells of ERU cases showed an activated phenotype with upregulation of GFAP and/or Vimentin, depending on the stage of inflammation. Immunohistochemistry revealed a decreased expression of GS and Kir 4.1 protein in diseased horses compared to controls. Western Blot analysis confirmed a significant (p<0.05) downregulation of potassium channel Kir 4.1 to 40% in diseased cases. Aquaporin 4 was expressed throughout Mueller cell bodies in retinas of healthy controls. This expression pattern changes in uveitic state to cell nuclei of outer nuclear layer. Overall expression of AQP4 increases in ERU.
Our data underscore the importance of Mueller glia cells in the pathogenesis of ERU. The downregulation of the Mueller cell membrane channels in the uveitic state might lead to imbalance of cell homeostasis and contribute to the ongoing cell damage, resulting in edema and loss of function.
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