AQUAPORIN-4 FACILITATES CELL PROLIFERATION IN RETINAL MÜLLER CELLS: IMPLICATIONS IN NEUROMYELITIS OPTICA

DI GIUSTO, GISELA; ECHEVERRIA, MIRIAM; ALAN WHITE; FORD, PAULA; VANINA NETTI; JUAN MANUEL FERNÁNDEZ; CAPURRO, CLAUDIA

Rosario

Congreso; Reunión Anual de la Sociedad Argentina de Fisiología; 2019

SAFIS

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