Aquaporin-4 facilitates cell proliferation in retinal Müller cells: Implications in Neuromyelitis Optica

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

Congreso; SAFIS 2019; 2019

Müller cells are involved in controlling extracellular homeostasis in the retina, regulating cell swelling by a mechanism known as regulatory volume decrease (RVD that depends on the efflux of solutes and water through Aquaporin-4 (AQP4). Müller cells also play a critical role in maintaining retinal structure and they are capable of re-entering the cell cycle and dedifferentiating. Although AQP4 was reported to facilitate cell proliferation in astrocytes, modulating cell volume during cell cycle progression, the participation of AQP4 in cell proliferation in Müller cells was not investigated. The aim of this study was to evaluate, using a novel specific inhibitor TGN-20, if AQP4 is involved in human Müller cell proliferation in physiological conditions. We then evaluated whether AQP4 endocytosis, induced by the autoantibody IgG-NMO present in the sera of patients with Neuromyelitis Optica (NMO), also affects cell proliferation to explain retinal injury observed in these patients.MIO-M1 human Müller cells were exposed to 100 nM TNG-020 (AQP4 inhibitor) or vehicle for x min, or to 1/50 dilution of IgG-NMO positive or control sera at 37°C for 12 hs. Cell volume was measured using fluorescence videomicroscopy and cell proliferation by cell count, cell cycle analysis by flow cytometry and/or BrdU incorporation by immunofluorescence. AQP4 inhibition with TGN-020 reduced osmotic water permeability (Pf in 104 cm/s) from 20.31.2 to 12.20.4 (n=5, p