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Aquaporin-4 Removal from the Plasma Membrane of Human Müller Cells by AQP4-IgG from Patients with Neuromyelitis Optica Induces Changes in Cell Volume Homeostasis: the First Step of Retinal Injury?

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Abstract

Aquaporin-4 (AQP4) is the target of the specific immunoglobulin G autoantibody (AQP4-IgG) produced in patients with neuromyelitis optica spectrum disorders (NMOSD). Previous studies demonstrated that AQP4-IgG binding to astrocytic AQP4 leads to cell-destructive lesions. However, the early physiopathological events in Müller cells in the retina are poorly understood. Here, we investigated the consequences of AQP4-IgG binding to AQP4 of Müller cells, previous to the inflammatory response, on two of AQP4’s key functions, cell volume regulation response (RVD) and cell proliferation, a process closely associated with changes in cell volume. Experiments were performed in a human retinal Müller cell line (MIO-M1) exposed to complement-inactivated sera from healthy volunteers or AQP4-IgG positive NMOSD patients. We evaluated AQP4 expression (immunofluorescence and western blot), water permeability coefficient, RVD, intracellular calcium levels and membrane potential changes during hypotonic shock (fluorescence videomicroscopy) and cell proliferation (cell count and BrdU incorporation). Our results showed that AQP4-IgG binding to AQP4 induces its partial internalization, leading to the decrease of the plasma membrane water permeability, a reduction of swelling-induced increase of intracellular calcium levels and the impairment of RVD in Müller cells. The loss of AQP4 from the plasma membrane induced by AQP4-IgG positive sera delayed Müller cells’ proliferation rate. We propose that Müller cell dysfunction after AQP4 removal from the plasma membrane by AQP4-IgG binding could be a non-inflammatory mechanism of retinal injury in vivo, altering cell volume homeostasis and cell proliferation and consequently, contributing to the physiopathology of NMOSD.

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Data Availability

The datasets generated and/or analyzed during the current study are available upon reasonable request.

References

  1. Pittock SJ, Lucchinetti CF (2016) Neuromyelitis optica and the evolving spectrum of autoimmune aquaporin-4 channelopathies: a decade later. Ann N Y Acad Sci 1366(1):20–39. https://doi.org/10.1111/nyas.12794

    Article  PubMed  Google Scholar 

  2. Lennon VA, Wingerchuk DM, Kryzer TJ, Pittock SJ, Lucchinetti CF, Fujihara K, Nakashima I, Weinshenker BG (2004) A serum autoantibody marker of neuromyelitis optica: distinction from multiple sclerosis. Lancet 364:2106–2112. https://doi.org/10.1016/S0140-6736(04)17551-X

    Article  CAS  PubMed  Google Scholar 

  3. Lennon VA, Kryzer TJ, Pittock SJ, Verkman AS, Hinson SR (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202:473–477. https://doi.org/10.1084/jem.20050304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Nagelhus EA, Ottersen OP (2013) Physiological roles of aquaporin-4 in brain. Physiol Rev 93:1543–1562. https://doi.org/10.1152/physrev.00011.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Bradl M, Reindl M, Lassmann H (2018) Mechanisms for lesion localization in neuromyelitis optica spectrum disorders. Curr Opin Neurol 31:325–333. https://doi.org/10.1097/WCO.0000000000000551

    Article  PubMed  PubMed Central  Google Scholar 

  6. Chang VTW, Chang HM (2020) Recent advances in the understanding of the pathophysiology of neuromyelitis optica spectrum disorder. Neuropathol Appl Neurobiol 46:199–218. https://doi.org/10.1111/nan.12574

    Article  CAS  PubMed  Google Scholar 

  7. Ratelade J, Verkman AS (2012) Neuromyelitis optica: aquaporin-4 based pathogenesis mechanisms and new therapies. Int J Biochem Cell Biol 44:1519–1530. https://doi.org/10.1016/j.biocel.2012.06.013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bennett JL, Owens GP (2017) Neuromyelitis optica: deciphering a complex immune-mediated astrocytopathy. J Neuroophthalmol 37:291–299. https://doi.org/10.1097/WNO.0000000000000508

    Article  PubMed  PubMed Central  Google Scholar 

  9. Reichenbach A, Bringmann A (2020) Glia of the human retina. Glia 68:768–796. https://doi.org/10.1002/glia.23727

    Article  PubMed  Google Scholar 

  10. Gelfand JM, Cree BA, Nolan R, Arnow S, Green AJ (2013) Microcystic inner nuclear layer abnormalities and neuromyelitis optica. JAMA Neurol 70:629–633. https://doi.org/10.1001/jamaneurol.2013.1832

    Article  PubMed  Google Scholar 

  11. Sotirchos ES, Saidha S, Byraiah G, Mealy MA, Ibrahim MA, Sepah YJ, Newsome SD, Ratchford JN et al (2013) In vivo identification of morphologic retinal abnormalities in neuromyelitis optica. Neurology 80:1406–1414. https://doi.org/10.1212/WNL.0b013e31828c2f7a

    Article  PubMed  PubMed Central  Google Scholar 

  12. Bennett JL, de Seze J, Lana-Peixoto M, Palace J, Waldman A, Schippling S, Tenembaum S, Banwell B et al (2015) Neuromyelitis optica and multiple sclerosis: Seeing differences through optical coherence tomography. Mult Scler 21:678–688. https://doi.org/10.1177/1352458514567216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Peng C, Wang W, Xu Q, Zhao S, Li H, Yang M, Cao S, Zhou H et al (2016) Structural alterations of segmented macular inner layers in aquaporin4-antibody-positive optic neuritis patients in a Chinese population. PLos One 11(6):e0157645. https://doi.org/10.1371/journal.pone.0157645

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Oertel FC, Kuchling J, Zimmermann H, Chien C, Schmidt F, Knier B, Bellmann-Strobl J, Korn T et al (2017) Microstructural visual system changes in AQP4-antibody-seropositive NMOSD. Neurol Neuroimmunol Neuroinflamm 4(3):e334. https://doi.org/10.1212/NXI.0000000000000334

    Article  PubMed  PubMed Central  Google Scholar 

  15. Filippatou AG, Vasileiou ES, He Y, Fitzgerald KC, Kalaitzidis G, Lambe J, Mealy MA, Levy M et al (2020) Evidence of subclinical quantitative retinal layer abnormalities in AQP4-IgG seropositive NMOSD. Mult Scler.https://doi.org/10.1177/1352458520977771

  16. Zeka B, Hastermann M, Kaufmann N, Schanda K, Pende M, Misu T, Rommer P, Fujihara K et al (2016) Aquaporin 4-specific T cells and NMO-IgG cause primary retinal damage in experimental NMO/SD. Acta Neuropathol Commun 4(1):82. https://doi.org/10.1186/s40478-016-0355-y

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Felix CM, Levin MH, Verkman AS (2016) Complement-independent retinal pathology produced by intravitreal injection of neuromyelitis optica immunoglobulin G. J Neuroinflammation 13(1):275. https://doi.org/10.1186/s12974-016-0746-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Pannicke T, Wurm A, Iandiev I, Hollborn M, Linnertz R, Binder DK, Kohen L, Wiedemann P et al (2010) Deletion of aquaporin-4 renders retinal glial cells more susceptible to osmotic stress. J Neurosci Res 88:2877–2888. https://doi.org/10.1002/jnr.22437

    Article  CAS  PubMed  Google Scholar 

  19. Fernández JM, Di Giusto G, Kalstein M, Melamud L, Rivarola V, Ford P, Capurro C (2013) Cell volume regulation in cultured human retinal Müller cells is associated with changes in transmembrane potential. PLoS One 8(2):e57268. https://doi.org/10.1371/journal.pone.0057268

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Netti V, Fernández J, Kalstein M, Pizzoni A, Di Giusto G, Rivarola V, Ford P, Capurro C (2017) TRPV4 contributes to resting membrane potential in retinal müller cells: implications in cell volume regulation. J Cell Biochem 118(8):2302–2313. https://doi.org/10.1002/jcb.25884

    Article  CAS  PubMed  Google Scholar 

  21. Netti V, Pizzoni A, Pérez-Domínguez M, Ford P, Pasantes-Morales H, Ramos-Mandujano G, Capurro C (2018) Release of taurine and glutamate contributes to cell volume regulation in human retinal Müller cells: differences in modulation by calcium. J Neurophysiol 120(3):973–984. https://doi.org/10.1152/jn.00725.2017

    Article  CAS  PubMed  Google Scholar 

  22. Benfenati V, Caprini M, Dovizio M, Mylonakou MN, Ferroni S, Ottersen OP, Amiry-Moghaddam M (2011) An aquaporin-4/transient receptor potential vanilloid 4 (AQP4/TRPV4) complex is essential for cell-volume control in astrocytes. Proc Natl Acad Sci 108(6):2563–2568. https://doi.org/10.1073/pnas.1012867108

    Article  PubMed  PubMed Central  Google Scholar 

  23. Jo AO, Ryskamp DA, Phuong TT, Verkman AS, Yarishkin O, MacAulay N, Križaj D (2015) TRPV4 and AQP4 channels synergistically regulate cell volume and calcium homeostasis in retinal müller glia. J Neurosci 35(39):13525–13537. https://doi.org/10.1523/JNEUROSCI.1987-15.2015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Fischer A, Reh T (2001) Müller glia are a potential source of neural regeneration in the postnatal chicken retina. Nat Neurosci 4:247–252. https://doi.org/10.1038/85090

    Article  CAS  PubMed  Google Scholar 

  25. Ooto S, Akagi T, Kageyama R, Akita J, Mandai M, Honda Y, Takahashi M (2004) Potential for neural regeneration after neurotoxic injury in the adult mammalian retina. Proc Natl Acad Sci 101(37):13654–13659. https://doi.org/10.1073/pnas.0402129101

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Giaume C, Kirchhoff F, Matute C, Reichenbach A, Verkhratsky A (2007) Glia: the fulcrum of brain diseases. Cell Death Differ 14(7):1324–1335. https://doi.org/10.1038/sj.cdd.4402144

    Article  CAS  PubMed  Google Scholar 

  27. Greco R, Bondanza A, Vago L, Moiola L, Rossi P, Furlan R, Martino G, Radaelli M et al (2014) Allogeneic hematopoietic stem cell transplantation for neuromyelitis optica. Ann Neurol 75(3):447–453. https://doi.org/10.1002/ana.24079

    Article  PubMed  Google Scholar 

  28. Kong H, Fan Y, Xie J, Ding J, Sha L, Shi X, Sun X, Hu G (2008) AQP4 knockout impairs proliferation, migration and neuronal differentiation of adult neural stem cells. J Cell Sci 121(Pt 24):4029–4036. https://doi.org/10.1242/jcs.035758

    Article  CAS  PubMed  Google Scholar 

  29. Li YB, Sun SR, Han XH (2016) Down-regulation of AQP4 inhibits proliferation, migration and invasion of human breast cancer cells. Folia Biol (Praha) 62(3):131–137

    Google Scholar 

  30. Di Giusto G, Flamenco P, Rivarola V, Fernández J, Melamud L, Ford P, Capurro C (2012) Aquaporin 2-increased renal cell proliferation is associated with cell volume regulation. J Cell Biochem 113(12):3721–3729. https://doi.org/10.1002/jcb.24246

    Article  CAS  PubMed  Google Scholar 

  31. Galán-Cobo A, Ramírez-Lorca R, Echevarría M (2016) Role of aquaporins in cell proliferation: What else beyond water permeability? Channels 10(3):185–201. https://doi.org/10.1080/19336950.2016.1139250

    Article  PubMed  PubMed Central  Google Scholar 

  32. Limb GA, Salt TE, Munro PM, Moss SE, Khaw PT (2002) In vitro characterization of a spontaneously immortalized human Muller cell line (MIO-M1). Invest Ophthalmol Vis Sci 43:864–869

    PubMed  Google Scholar 

  33. Wingerchuk DM, Banwell B, Bennett JL, Cabre P, Carroll W, Chitnis T, de Seze J, Fujihara K et al (2015) International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology 85(2):177–189. https://doi.org/10.1212/WNL.0000000000001729

    Article  PubMed  PubMed Central  Google Scholar 

  34. Melamud L, Fernandez JM, Rivarola V, Di Giusto G, Ford P, Villa A, Capurro C (2012) Neuromyelitis Optica Immunoglobulin G present in sera from neuromyelitis optica patients affects aquaporin-4 expression and water permeability of the astrocyte plasma membrane. J Neurosci Res 90:1240–1248. https://doi.org/10.1002/jnr.22822

    Article  CAS  PubMed  Google Scholar 

  35. García-Miranda P, Morón-Civanto FJ, Martínez-Olivo MDM, Suárez-Luna N, Ramírez-Lorca R, Lebrato-Hernández L, Lamas-Pérez R, Navarro G et al (2019) Predictive value of serum antibodies and point mutations of AQP4, AQP1 and MOG in a cohort of Spanish patients with neuromyelitis optica spectrum disorders. Int J Mol Sci 20(22):5810. https://doi.org/10.3390/ijms20225810

    Article  CAS  PubMed Central  Google Scholar 

  36. Hinson SR, Pittock SJ, Lucchinetti CF, Roemer SF, Fryer JP, Kryzer TJ, Lennon VA (2007) Pathogenic potential of IgG binding to water channel extracellular domain in neuromyelitis optica. Neurology 69:2221–2231. https://doi.org/10.1212/01.WNL.0000289761.64862.ce

    Article  CAS  PubMed  Google Scholar 

  37. Kida T, Oku H, Horie T, Fukumoto M, Okuda Y, Morishita S, Ikeda T (2017) Implication of VEGF and aquaporin 4 mediating Müller cell swelling to diabetic retinal edema. Graefes Arch Clin Exp Ophthalmol 255(6):1149–1157. https://doi.org/10.1007/s00417-017-3631-z

    Article  CAS  PubMed  Google Scholar 

  38. Sachs AN, Pisitkun T, Hoffert JD, Yu MJ, Knepper MA (2008) LC-MS/MS analysis of differential centrifugation fractions from native inner medullary collecting duct of rat. Am J Physiol Renal Physiol 295(6):F1799–F1806. https://doi.org/10.1152/ajprenal.90510.2008

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Hinson SR, Romero MF, Popescu BF, Lucchinetti CF, Fryer JP, Wolburg H, Fallier-Becker P, Noell S et al (2012) Molecular outcomes of neuromyelitis optica (NMO)-IgG binding to aquaporin-4 in astrocytes. Proc Natl Acad Sci 109(4):1245–1250. https://doi.org/10.1073/pnas.1109980108

    Article  PubMed  Google Scholar 

  40. Green AJ, Cree BA (2009) Distinctive retinal nerve fibre layer and vascular changes in neuromyelitis optica following optic neuritis. J Neurol Neurosurg Psychiatry 80(9):1002–1005. https://doi.org/10.1136/jnnp.2008.166207

    Article  CAS  PubMed  Google Scholar 

  41. Levin MH, Bennett JL, Verkman AS (2013) Optic neuritis in neuromyelitis optica. Prog Retin Eye Res 36:159–171. https://doi.org/10.1016/j.preteyeres.2013.03.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Toft-Bertelsen TL, Larsen BR, Christensen SK, Khandelia H, Waagepetersen HS, MacAulay N (2020) Clearance of activity-evoked K+ transients and associated glia cell swelling occur independently of AQP4: a study with an isoform-selective AQP4 inhibitor. Glia 69(1):28–41. https://doi.org/10.1002/glia.23851

    Article  CAS  PubMed  Google Scholar 

  43. De Bellis M, Pisani F, Mola MG, Rosito S, Simone L, Buccoliero C, Trojano M, Nicchia GP et al (2017) Translational readthrough generates new astrocyte AQP4 isoforms that modulate supramolecular clustering, glial endfeet localization, and water transport. Glia 65(5):790–803. https://doi.org/10.1002/glia.23126

    Article  PubMed  Google Scholar 

  44. Lisjak M, Potokar M, Zorec R, Jorgačevski J (2020) Indirect Role of AQP4b and AQP4d Isoforms in Dynamics of Astrocyte Volume and Orthogonal Arrays of Particles. Cells 9(3):735. https://doi.org/10.3390/cells9030735

    Article  CAS  PubMed Central  Google Scholar 

  45. Jorgačevski J, Zorec R, Potokar M (2020) Insights into Cell Surface Expression, Supramolecular Organization, and Functions of Aquaporin 4 Isoforms in Astrocytes. Cells 9(12):2622. https://doi.org/10.3390/cells9122622

    Article  CAS  PubMed Central  Google Scholar 

  46. Palazzo C, Buccoliero C, Mola MG, Abbrescia P, Nicchia GP, Trojano M, Frigeri A (2019) AQP4ex is crucial for the anchoring of AQP4 at the astrocyte end-feet and for neuromyelitis optica antibody binding. Acta Neuropathol Commun 7(1):51. https://doi.org/10.1186/s40478-019-0707-5

    Article  PubMed  PubMed Central  Google Scholar 

  47. Lisjak M, Potokar M, Rituper B, Jorgačevski J, Zorec R (2017) AQP4e-based orthogonal arrays regulate rapid cell volume changes in astrocytes. J Neurosci 37(44):10748–10756. https://doi.org/10.1523/JNEUROSCI.0776-17.2017

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Thrane AS, Rappold PM, Fujita T, Torres A, Bekar LK, Takano T, Peng W, Wang F et al (2010) Critical role of aquaporin-4 (AQP4) in astrocytic Ca2+ signaling events elicited by cerebral edema. Proc Natl Acad Sci 108(2):846–851. https://doi.org/10.1073/pnas.1015217108

    Article  PubMed  PubMed Central  Google Scholar 

  49. Galizia L, Flamenco MP, Rivarola V, Capurro C, Ford P (2008) Role of AQP2 in activation of calcium entry by hypotonicity: implications in cell volume regulation. Am J Physiol Renal Physiol 294(3):F582–F590. https://doi.org/10.1152/ajprenal.00427.2007

    Article  CAS  PubMed  Google Scholar 

  50. Mola MG, Sparaneo A, Gargano CD, Spray DC, Svelto M, Frigeri A, Scemes E, Nicchia GP (2016) The speed of swelling kinetics modulates cell volume regulation and calcium signaling in astrocytes: a different point of view on the role of aquaporins. Glia 64(1):139–154. https://doi.org/10.1002/glia.22921

    Article  PubMed  Google Scholar 

  51. Fort PE, Sene A, Pannicke T, Roux MJ, Forster V, Mornet D, Nudel U, Yaffe D et al (2008) Kir4.1 and AQP4 associate with Dp71- and utrophin-DAPs complexes in specific and defined microdomains of Müller retinal glial cell membrane. Glia 56(6):597–610. https://doi.org/10.1002/glia.20633

    Article  PubMed  Google Scholar 

  52. Nicchia GP, Pisani F, Simone L, Cibelli A, Mola MG, Dal Monte M, Frigeri A, Bagnoli P et al (2016) Glio-vascular modifications caused by Aquaporin-4 deletion in the mouse retina. Exp Eye Res 146:259–268. https://doi.org/10.1016/j.exer.2016.03.019

    Article  CAS  PubMed  Google Scholar 

  53. Di Giusto G, Pizzoni A, Rivarola V, Beltramone N, White A, Ford P, Capurro C (2019) Aquaporin-2 and Na+/H+ exchanger isoform 1 modulate the efficiency of renal cell migration. J Cell Physiol 235(5):4443–4454. https://doi.org/10.1002/jcp.29320

    Article  CAS  PubMed  Google Scholar 

  54. Takai Y, Misu T, Suzuki H, Takahashi T, Okada H, Tanaka S, Okita K, Sasou S et al (2021) Staging of astrocytopathy and complement activation in neuromyelitis optica spectrum disorders. Brain.https://doi.org/10.1093/brain/awab102

  55. Zannetti A, Benga G, Brunetti A, Napolitano F, Avallone L, Pelagalli A (2020) Role of Aquaporins in the Physiological Functions of Mesenchymal Stem Cells. Cells 9(12):2678. https://doi.org/10.3390/cells9122678

    Article  CAS  PubMed Central  Google Scholar 

  56. Yang C, Yang Y, Ma L, Zhang GX, Shi FD, Yan Y, Chang G (2019) Study of the cytological features of bone marrow mesenchymal stem cells from patients with neuromyelitis optica. Int J Mol Med 43(3):1395–1405. https://doi.org/10.3892/ijmm.2019.4056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. You Y, Zhu L, Zhang T, Shen T, Fontes A, Yiannikas C, Parratt J, Barton J et al (2019) Evidence of Müller glial dysfunction in patients with aquaporin-4 immunoglobulin g-positive neuromyelitis optica spectrum disorder. Ophthalmology 126(6):801–810. https://doi.org/10.1016/j.ophtha.2019.01.016

    Article  PubMed  Google Scholar 

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Acknowledgements

The authors thank Dr. Astrid Limb (University College London, London, UK) for providing the human Müller Cell Line (MIO-M1) and Natalia Beltramone, Germán La Iacona, and Ricardo Dorr for technical assistance.

Funding

This study was supported by grants from the University of Buenos Aires (UBA-SECYT, 20020130100682BA, 2018–2021, Argentina) to Claudia Capurro; the Agencia Nacional de Promoción Científica y Tecnológica (ANPCyT 2019–01707, Argentina) to Claudia Capurro and the Spanish Ministry of Economy and Competitiveness, co-financed by the Carlos III Health Institute (ISCIII) and European Regional Development Fund (FEDER, PI16/00493) to Miriam Echevarría.

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Authors and Affiliations

  1. Departamento de Ciencias Fisiológicas, Laboratorio de Biomembranas, Facultad de Medicina, Instituto de Fisiología y Biofísica “Bernardo Houssay” (IFIBIO‐HOUSSAY), Consejo Nacional de Investigaciones Científicas Y Técnicas (CONICET), Universidad de Buenos Aires, Buenos Aires, Argentina

    Vanina Netti, Juan Fernández, Gisela Di Giusto, Paula Ford & Claudia Capurro

  2. Servicio de Neurología, Centro Universitario de Neurología Dr. J.M. Ramos Mejía, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

    Luciana Melamud

  3. Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC, Universidad de Sevilla, Seville, Spain

    Pablo Garcia-Miranda & Miriam Echevarría

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  1. Vanina Netti
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Contributions

Claudia Capurro and Vanina Netti designed the study, interpreted the data, and coordinated the project. Vanina Netti and Juan Fernández conducted the experiments, data collection, and statistical analysis. Luciana Melamud provided consultation for clinical relevance. Pablo García-Miranda and Gisela Di Giusto provided consultation for methodology and conducted some experiments. Paula Ford and Miriam Echevarria contributed to the disign stages and interpretation of the research. The manuscript was written by Claudia Capurro and Vanina Netti and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Correspondence to Claudia Capurro.

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The study was approved by the Institutional Ethics Committee for Research in Translational Medicine Alberto C. Taquini of the School of Medicine, University of Buenos Aires (IATIMET, N°: PICT2019/10707 version 1.0), which is in compliance with the International Guideline for Human Research protection as laid down in the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

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Netti, V., Fernández, J., Melamud, L. et al. Aquaporin-4 Removal from the Plasma Membrane of Human Müller Cells by AQP4-IgG from Patients with Neuromyelitis Optica Induces Changes in Cell Volume Homeostasis: the First Step of Retinal Injury?. Mol Neurobiol 58, 5178–5193 (2021). https://doi.org/10.1007/s12035-021-02491-x

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