Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica

Autores
Netti, Vanina Alejandra; White, Alan; Di Giusto, Gisela; Fernández, Juan; Ford, Paula; Echevarría, Miriam; Capurro, Claudia Graciela
Año de publicación
2020
Idioma
inglés
Tipo de recurso
documento de conferencia
Estado
versión publicada
Descripción
Müller cells are involved in controlling extracellular homeostasis in the retina, regulating cell swelling by a regulatory volume decrease (RVD) mechanism that depends on the efflux of solutes and water through Aquaporin-4 (AQP4). Müller cells are also important for retinal integrity, as they respond to injury by re-entering the cell cycle for tissue repair. Since AQP4 was reported to modulate cell volume during cell cycle progression and facilitate proliferation in astrocytes, the aim of this study was to evaluate, using the novel inhibitor TGN-020, if AQP4 was involved in human Müller cells? proliferation in physiological conditions. Considering that AQP4 is the target of autoantibody IgG-NMO present in the sera of patients with Neuromyelitis Optica (NMO), we also evaluated if cell proliferation was altered in the presence of IgG-NMO. MIO-M1 human Müller cells were exposed to 100 nM TNG-020 or vehicle or to 1/50 dilution of IgG-NMO positive or control sera. Cell volume (videomicroscopy) and cell proliferation (cell count, cell cycle analysis by flow cytometry and BrdU incorporation by immunofluorescence) were measured. AQP4 inhibition with TGN-020 reduced osmotic water permeability (Pf, µm/s) from 20.3±1.2 to 12.2±0.4 (n=5, p<0.001) and %RVD 15min from 54±4 to 17±3 (n=5, p<0.001). MIO-M1 cell proliferation was decreased by TGN-020 (doubling time in hours, control vs. TGN-020: 31±1 vs. 40±3, n=4, p<0.05) without affecting cell viability. TGN-020 also increased the % of cells in G1/G0 phase, decreased the S phase of cell cycle and reduced BrdU incorporation by 20%. IgG-NMO positive sera decreased AQP4 plasma membrane expression in MIO-M1 cells, reducing Pf from 22.4±1.5 to 15.9±0.6 µm/s (n=6, p<0.001) and %RVD 15min from 66±5 to 48±4 (n=6, p<0.005), as well as cell proliferation (doubling time in hours, control vs. IgG-NMO: 59±5 vs. 86±4, n=3, p<0.05) in comparison to control sera. We propose that inhibition or removal of AQP4 from the plasma membrane reduces AQP4-mediated water permeability altering cell proliferation. This is of particular importance in NMO, as the decreased ability of Müller cells to proliferate may affect retinal tissue repair.
Fil: Netti, Vanina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: White, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Di Giusto, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Fernández, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Ford, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Echevarría, Miriam. Universidad de Sevilla; España
Fil: Capurro, Claudia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Reunión Anual de la Sociedad Argentina de Fisiología
Rosario
Argentina
Sociedad Argentina de Fisiologia
Materia
AQUAPORIN-44
RETINAL MULLER CELLS
CELL PROLIFERATION
NEUROMYELITIS OPTICA
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/183833
Acceder
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oai_identifier_str oai:ri.conicet.gov.ar:11336/183833
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis opticaNetti, Vanina AlejandraWhite, AlanDi Giusto, GiselaFernández, JuanFord, PaulaEchevarría, MiriamCapurro, Claudia GracielaAQUAPORIN-44RETINAL MULLER CELLSCELL PROLIFERATIONNEUROMYELITIS OPTICAhttps://purl.org/becyt/ford/3.1https://purl.org/becyt/ford/3Müller cells are involved in controlling extracellular homeostasis in the retina, regulating cell swelling by a regulatory volume decrease (RVD) mechanism that depends on the efflux of solutes and water through Aquaporin-4 (AQP4). Müller cells are also important for retinal integrity, as they respond to injury by re-entering the cell cycle for tissue repair. Since AQP4 was reported to modulate cell volume during cell cycle progression and facilitate proliferation in astrocytes, the aim of this study was to evaluate, using the novel inhibitor TGN-020, if AQP4 was involved in human Müller cells? proliferation in physiological conditions. Considering that AQP4 is the target of autoantibody IgG-NMO present in the sera of patients with Neuromyelitis Optica (NMO), we also evaluated if cell proliferation was altered in the presence of IgG-NMO. MIO-M1 human Müller cells were exposed to 100 nM TNG-020 or vehicle or to 1/50 dilution of IgG-NMO positive or control sera. Cell volume (videomicroscopy) and cell proliferation (cell count, cell cycle analysis by flow cytometry and BrdU incorporation by immunofluorescence) were measured. AQP4 inhibition with TGN-020 reduced osmotic water permeability (Pf, µm/s) from 20.3±1.2 to 12.2±0.4 (n=5, p<0.001) and %RVD 15min from 54±4 to 17±3 (n=5, p<0.001). MIO-M1 cell proliferation was decreased by TGN-020 (doubling time in hours, control vs. TGN-020: 31±1 vs. 40±3, n=4, p<0.05) without affecting cell viability. TGN-020 also increased the % of cells in G1/G0 phase, decreased the S phase of cell cycle and reduced BrdU incorporation by 20%. IgG-NMO positive sera decreased AQP4 plasma membrane expression in MIO-M1 cells, reducing Pf from 22.4±1.5 to 15.9±0.6 µm/s (n=6, p<0.001) and %RVD 15min from 66±5 to 48±4 (n=6, p<0.005), as well as cell proliferation (doubling time in hours, control vs. IgG-NMO: 59±5 vs. 86±4, n=3, p<0.05) in comparison to control sera. We propose that inhibition or removal of AQP4 from the plasma membrane reduces AQP4-mediated water permeability altering cell proliferation. This is of particular importance in NMO, as the decreased ability of Müller cells to proliferate may affect retinal tissue repair.Fil: Netti, Vanina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: White, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Di Giusto, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Fernández, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Ford, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaFil: Echevarría, Miriam. Universidad de Sevilla; EspañaFil: Capurro, Claudia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; ArgentinaReunión Anual de la Sociedad Argentina de FisiologíaRosarioArgentinaSociedad Argentina de FisiologiaSociedad Argentina de Fisiología2020info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObjectReuniónBookhttp://purl.org/coar/resource_type/c_5794info:ar-repo/semantics/documentoDeConferenciaapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/183833Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica; Reunión Anual de la Sociedad Argentina de Fisiología; Rosario; Argentina; 2019; 1-2CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://safisiol.org.ar/wp-content/uploads/2019/10/SAFIS2019.pdfNacionalinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-10T13:03:15Zoai:ri.conicet.gov.ar:11336/183833instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-10 13:03:16.254CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica
title Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica
spellingShingle Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica
Netti, Vanina Alejandra
AQUAPORIN-44
RETINAL MULLER CELLS
CELL PROLIFERATION
NEUROMYELITIS OPTICA
title_short Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica
title_full Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica
title_fullStr Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica
title_full_unstemmed Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica
title_sort Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica
dc.creator.none.fl_str_mv Netti, Vanina Alejandra
White, Alan
Di Giusto, Gisela
Fernández, Juan
Ford, Paula
Echevarría, Miriam
Capurro, Claudia Graciela
author Netti, Vanina Alejandra
author_facet Netti, Vanina Alejandra
White, Alan
Di Giusto, Gisela
Fernández, Juan
Ford, Paula
Echevarría, Miriam
Capurro, Claudia Graciela
author_role author
author2 White, Alan
Di Giusto, Gisela
Fernández, Juan
Ford, Paula
Echevarría, Miriam
Capurro, Claudia Graciela
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv AQUAPORIN-44
RETINAL MULLER CELLS
CELL PROLIFERATION
NEUROMYELITIS OPTICA
topic AQUAPORIN-44
RETINAL MULLER CELLS
CELL PROLIFERATION
NEUROMYELITIS OPTICA
purl_subject.fl_str_mv https://purl.org/becyt/ford/3.1
https://purl.org/becyt/ford/3
dc.description.none.fl_txt_mv Müller cells are involved in controlling extracellular homeostasis in the retina, regulating cell swelling by a regulatory volume decrease (RVD) mechanism that depends on the efflux of solutes and water through Aquaporin-4 (AQP4). Müller cells are also important for retinal integrity, as they respond to injury by re-entering the cell cycle for tissue repair. Since AQP4 was reported to modulate cell volume during cell cycle progression and facilitate proliferation in astrocytes, the aim of this study was to evaluate, using the novel inhibitor TGN-020, if AQP4 was involved in human Müller cells? proliferation in physiological conditions. Considering that AQP4 is the target of autoantibody IgG-NMO present in the sera of patients with Neuromyelitis Optica (NMO), we also evaluated if cell proliferation was altered in the presence of IgG-NMO. MIO-M1 human Müller cells were exposed to 100 nM TNG-020 or vehicle or to 1/50 dilution of IgG-NMO positive or control sera. Cell volume (videomicroscopy) and cell proliferation (cell count, cell cycle analysis by flow cytometry and BrdU incorporation by immunofluorescence) were measured. AQP4 inhibition with TGN-020 reduced osmotic water permeability (Pf, µm/s) from 20.3±1.2 to 12.2±0.4 (n=5, p<0.001) and %RVD 15min from 54±4 to 17±3 (n=5, p<0.001). MIO-M1 cell proliferation was decreased by TGN-020 (doubling time in hours, control vs. TGN-020: 31±1 vs. 40±3, n=4, p<0.05) without affecting cell viability. TGN-020 also increased the % of cells in G1/G0 phase, decreased the S phase of cell cycle and reduced BrdU incorporation by 20%. IgG-NMO positive sera decreased AQP4 plasma membrane expression in MIO-M1 cells, reducing Pf from 22.4±1.5 to 15.9±0.6 µm/s (n=6, p<0.001) and %RVD 15min from 66±5 to 48±4 (n=6, p<0.005), as well as cell proliferation (doubling time in hours, control vs. IgG-NMO: 59±5 vs. 86±4, n=3, p<0.05) in comparison to control sera. We propose that inhibition or removal of AQP4 from the plasma membrane reduces AQP4-mediated water permeability altering cell proliferation. This is of particular importance in NMO, as the decreased ability of Müller cells to proliferate may affect retinal tissue repair.
Fil: Netti, Vanina Alejandra. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: White, Alan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Di Giusto, Gisela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Fernández, Juan. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Ford, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Fil: Echevarría, Miriam. Universidad de Sevilla; España
Fil: Capurro, Claudia Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Fisiología y Biofísica Bernardo Houssay. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Fisiología y Biofísica Bernardo Houssay; Argentina
Reunión Anual de la Sociedad Argentina de Fisiología
Rosario
Argentina
Sociedad Argentina de Fisiologia
description Müller cells are involved in controlling extracellular homeostasis in the retina, regulating cell swelling by a regulatory volume decrease (RVD) mechanism that depends on the efflux of solutes and water through Aquaporin-4 (AQP4). Müller cells are also important for retinal integrity, as they respond to injury by re-entering the cell cycle for tissue repair. Since AQP4 was reported to modulate cell volume during cell cycle progression and facilitate proliferation in astrocytes, the aim of this study was to evaluate, using the novel inhibitor TGN-020, if AQP4 was involved in human Müller cells? proliferation in physiological conditions. Considering that AQP4 is the target of autoantibody IgG-NMO present in the sera of patients with Neuromyelitis Optica (NMO), we also evaluated if cell proliferation was altered in the presence of IgG-NMO. MIO-M1 human Müller cells were exposed to 100 nM TNG-020 or vehicle or to 1/50 dilution of IgG-NMO positive or control sera. Cell volume (videomicroscopy) and cell proliferation (cell count, cell cycle analysis by flow cytometry and BrdU incorporation by immunofluorescence) were measured. AQP4 inhibition with TGN-020 reduced osmotic water permeability (Pf, µm/s) from 20.3±1.2 to 12.2±0.4 (n=5, p<0.001) and %RVD 15min from 54±4 to 17±3 (n=5, p<0.001). MIO-M1 cell proliferation was decreased by TGN-020 (doubling time in hours, control vs. TGN-020: 31±1 vs. 40±3, n=4, p<0.05) without affecting cell viability. TGN-020 also increased the % of cells in G1/G0 phase, decreased the S phase of cell cycle and reduced BrdU incorporation by 20%. IgG-NMO positive sera decreased AQP4 plasma membrane expression in MIO-M1 cells, reducing Pf from 22.4±1.5 to 15.9±0.6 µm/s (n=6, p<0.001) and %RVD 15min from 66±5 to 48±4 (n=6, p<0.005), as well as cell proliferation (doubling time in hours, control vs. IgG-NMO: 59±5 vs. 86±4, n=3, p<0.05) in comparison to control sera. We propose that inhibition or removal of AQP4 from the plasma membrane reduces AQP4-mediated water permeability altering cell proliferation. This is of particular importance in NMO, as the decreased ability of Müller cells to proliferate may affect retinal tissue repair.
publishDate 2020
dc.date.none.fl_str_mv 2020
dc.type.none.fl_str_mv info:eu-repo/semantics/publishedVersion
info:eu-repo/semantics/conferenceObject
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Book
http://purl.org/coar/resource_type/c_5794
info:ar-repo/semantics/documentoDeConferencia
status_str publishedVersion
format conferenceObject
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/183833
Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica; Reunión Anual de la Sociedad Argentina de Fisiología; Rosario; Argentina; 2019; 1-2
CONICET Digital
CONICET
url http://hdl.handle.net/11336/183833
identifier_str_mv Aquaporin-4 facilitates cell proliferation in retinal müller cells: implications in neuromyelitis optica; Reunión Anual de la Sociedad Argentina de Fisiología; Rosario; Argentina; 2019; 1-2
CONICET Digital
CONICET
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language eng
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dc.publisher.none.fl_str_mv Sociedad Argentina de Fisiología
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