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.
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
Researcher Affiliations
- Department of Veterinary Sciences, Institute of Animal Physiology, Ludwig-Maximilians University, München, Germany.
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.- Fleischer AB, Amann B, von Toerne C, Degroote RL, Schmalen A, Weißer T, Hauck SM, Deeg CA. Differential Expression of ARG1 and MRC2 in Retinal Müller Glial Cells During Autoimmune Uveitis. Biomolecules 2025 Feb 14;15(2).
- Han C, Li Y, Zheng X, Zhang X, Li G, Zhao L, Chen Z, Yang Y, Zhang W. AQP4- and Kir4.1-Mediated Müller Cell Oedema Is Involved in Retinal Injury Induced By Hypobaric Hypoxia. Mol Neurobiol 2025 Feb;62(2):2012-2022.
- Carrero L, Antequera D, Alcalde I, Megias D, Ordoñez-Gutierrez L, Gutierrez C, Merayo-Lloves J, Wandosell F, Municio C, Carro E. Altered Clock Gene Expression in Female APP/PS1 Mice and Aquaporin-Dependent Amyloid Accumulation in the Retina. Int J Mol Sci 2023 Oct 27;24(21).
- Ruff A, Tezel A, Tezel TH. Anatomical and functional correlates of cystic macular edema in retinitis pigmentosa. PLoS One 2022;17(10):e0276629.
- Lorenz L, Hirmer S, Schmalen A, Hauck SM, Deeg CA. Cell Surface Profiling of Retinal Müller Glial Cells Reveals Association to Immune Pathways after LPS Stimulation. Cells 2021 Mar 23;10(3).
- Degroote RL, Deeg CA. Immunological Insights in Equine Recurrent Uveitis. Front Immunol 2020;11:609855.
- Batioglu F, Yanık Ö, Demirel S, Özmert E. Pseudophakic macular edema involving epiretinal proliferation associated with macular hole. Indian J Ophthalmol 2020 Nov;68(11):2599-2601.
- Fischer RA, Roux AL, Wareham LK, Sappington RM. Pressure-dependent modulation of inward-rectifying K(+) channels: implications for cation homeostasis and K(+) dynamics in glaucoma. Am J Physiol Cell Physiol 2019 Aug 1;317(2):C375-C389.
- Liu X, Roux MJ, Picaud S, Keller D, Sauer A, Heitz P, Prévost G, Gaucher D. Panton-Valentine Leucocidin Proves Direct Neuronal Targeting and Its Early Neuronal and Glial Impacts a Rabbit Retinal Explant Model. Toxins (Basel) 2018 Nov 4;10(11).
- Zayas-Santiago A, Ríos DS, Zueva LV, Inyushin MY. Localization of αA-Crystallin in Rat Retinal Müller Glial Cells and Photoreceptors. Microsc Microanal 2018 Oct;24(5):545-552.
- Schirmer L, Möbius W, Zhao C, Cruz-Herranz A, Ben Haim L, Cordano C, Shiow LR, Kelley KW, Sadowski B, Timmons G, Pröbstel AK, Wright JN, Sin JH, Devereux M, Morrison DE, Chang SM, Sabeur K, Green AJ, Nave KA, Franklin RJ, Rowitch DH. Oligodendrocyte-encoded Kir4.1 function is required for axonal integrity. Elife 2018 Sep 11;7.
- Agte S, Savvinov A, Karl A, Zayas-Santiago A, Ulbricht E, Makarov VI, Reichenbach A, Bringmann A, Skatchkov SN. Müller glial cells contribute to dim light vision in the spectacled caiman (Caiman crocodilus fuscus): Analysis of retinal light transmission. Exp Eye Res 2018 Aug;173:91-108.
- Amann B, Kleinwort KJ, Hirmer S, Sekundo W, Kremmer E, Hauck SM, Deeg CA. Expression and Distribution Pattern of Aquaporin 4, 5 and 11 in Retinas of 15 Different Species. Int J Mol Sci 2016 Jul 16;17(7).
- Deeg CA, Amann B, Lutz K, Hirmer S, Lutterberg K, Kremmer E, Hauck SM. Aquaporin 11, a regulator of water efflux at retinal Müller glial cell surface decreases concomitant with immune-mediated gliosis. J Neuroinflammation 2016 Apr 23;13(1):89.
- Lopez IA, Acuna D, Edmond J. Modulatory Effects of Mild Carbon Monoxide Exposure in the Developing Mouse Cochlea. Neurochem Res 2017 Jan;42(1):151-165.
- Dharmarajan S, Gurel Z, Wang S, Sorenson CM, Sheibani N, Belecky-Adams TL. Bone morphogenetic protein 7 regulates reactive gliosis in retinal astrocytes and Müller glia. Mol Vis 2014;20:1085-108.
- Zayas-Santiago A, Agte S, Rivera Y, Benedikt J, Ulbricht E, Karl A, Dávila J, Savvinov A, Kucheryavykh Y, Inyushin M, Cubano LA, Pannicke T, Veh RW, Francke M, Verkhratsky A, Eaton MJ, Reichenbach A, Skatchkov SN. Unidirectional photoreceptor-to-Müller glia coupling and unique K+ channel expression in Caiman retina. PLoS One 2014;9(5):e97155.
- Schey KL, Wang Z, L Wenke J, Qi Y. Aquaporins in the eye: expression, function, and roles in ocular disease. Biochim Biophys Acta 2014 May;1840(5):1513-23.
- Swadzba ME, Hauck SM, Naim HY, Amann B, Deeg CA. Retinal glycoprotein enrichment by concanavalin a enabled identification of novel membrane autoantigen synaptotagmin-1 in equine recurrent uveitis. PLoS One 2012;7(12):e50929.
- Szober CM, Hauck SM, Euler KN, Fröhlich KJ, Alge-Priglinger C, Ueffing M, Deeg CA. Profound re-organization of cell surface proteome in equine retinal pigment epithelial cells in response to in vitro culturing. Int J Mol Sci 2012 Oct 31;13(11):14053-72.
- Kumari SS, Varadaraj M, Yerramilli VS, Menon AG, Varadaraj K. Spatial expression of aquaporin 5 in mammalian cornea and lens, and regulation of its localization by phosphokinase A. Mol Vis 2012;18:957-67.
- Deeg CA, Eberhardt C, Hofmaier F, Amann B, Hauck SM. Osteopontin and fibronectin levels are decreased in vitreous of autoimmune uveitis and retinal expression of both proteins indicates ECM re-modeling. PLoS One 2011;6(12):e27674.
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