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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?
Netti, Vanina; Fernández, Juan; Melamud, Luciana; Garcia-Miranda, Pablo; Di Giusto, Gisela; Ford, Paula; Echevarría, Miriam; Capurro, Claudia.
Afiliação
  • Netti V; 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.
  • Fernández J; 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.
  • Melamud L; Servicio de Neurología, Centro Universitario de Neurología Dr. J.M. Ramos Mejía, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
  • Garcia-Miranda P; Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC, Universidad de Sevilla, Seville, Spain.
  • Di Giusto G; 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.
  • Ford P; 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.
  • Echevarría M; Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC, Universidad de Sevilla, Seville, Spain.
  • Capurro C; 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. capurroclaudi
Mol Neurobiol ; 58(10): 5178-5193, 2021 Oct.
Article em En | MEDLINE | ID: mdl-34263427
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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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Retina / Imunoglobulina G / Membrana Celular / Neuromielite Óptica / Aquaporina 4 / Células Ependimogliais Limite: Humans Idioma: En Revista: Mol Neurobiol Assunto da revista: BIOLOGIA MOLECULAR / NEUROLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Retina / Imunoglobulina G / Membrana Celular / Neuromielite Óptica / Aquaporina 4 / Células Ependimogliais Limite: Humans Idioma: En Revista: Mol Neurobiol Assunto da revista: BIOLOGIA MOLECULAR / NEUROLOGIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Argentina País de publicação: Estados Unidos