Neuromyelitis optica immunoglobulin G targets AQP4 expressed in retinal M?uller cells affecting cell volume homeostasis

FERNÁNDEZ, JUAN MANUEL; FORD, PAULA; NETTI, VANINA; RIVAROLA, VALERIA; CAPURRO, CLAUDIA; DI GIUSTO, GISELA; MELAMUD, LUCIANA

París

Congreso; 2017 ISN-ESN Meeting; 2017

International Society for Neurochemestry

The current study evaluates if the water channel AQP4, highly expressed in Müller cells in the retina, is a pathogenic ocular target of specific serum immunoglobulin G autoantibody (NMOIgG) produced in patients with Neuromyelitis Optica. Particularly we investigated the consequences of NMO‐IgG binding to AQP4 on plasma membrane water permeability and cell volume homeostasis. Studies were performed in a human retinal Müller cell line (MIO‐M1), a good model that maintains important functional characteristics of Müller cells. To avoid or to facilitate AQP4 down‐regulation, cells were exposed to inactivated control or positive NMOIgG sera in two different situations (1 hr at 4°C or 12 hr at 37°C). AQP4 expression was detected by immunofluorescence studies using a polyclonal anti‐AQP4 antibody and the water permeability coefficient and cell volume regulation capacity were evaluated by fluorescence videomicroscopy. Our results showed that immediate NMO‐IgG binding to AQP4 is not enough to affect water channel´s activity. However, long‐term exposure to NMO patient sera clearly induced a loss of AQP4 signal from plasma membrane, along with a significant reduction of water permeability and the capacity to regulate cell volume after an osmotic swelling (RVD), a key function of Müller cells. These data demonstrate that NMO‐IgG targets Müller cells AQP4, affecting its expression and its function, and subsequently cell homeostasis. Therefore, we propose that water permeability reduction after NMO‐IgG binding to AQP4 in Müller cells contributes to retinal cell damage and tissue edema observed in NMO patients.