Neuromyelitis Optica Immunoglobulin G targets AQP4 expressed in Retinal Müller cells affecting Cell Volume Homeostasis

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

Paris

Congreso; Congress of The International Society for Neurochemestry; 2017

ISN

The currentstudy evaluates if the water channel AQP4, highly expressed in Müller cells in theretina, is a pathogenic ocular target of specific serum immunoglobulin G autoantibody(NMO ‐ IgG) produced in patients with Neuromyelitis Optica. Particularly we investigatedthe consequences of NMO ‐ IgG binding to AQP4 on plasma membrane water permeabilityand cell volume homeostasis. Studies were performed in a human retinal Müller cellline (MIO ‐ M1), a good model that maintains important functional characteristicsof Müller cells. To avoid or to facilitate AQP4 down ‐ regulation, cells were exposedto inactivated control or positive NMO ‐ IgG sera in two different situations (1hr at 4°C or 12 hr at 37°C). AQP4 expression was detected by immunofluorescencestudies using a polyclonal anti ‐ AQP4 antibody and the water permeability coefficientand cell volume regulation capacity were evaluated by fluorescence videomicroscopy.Our results showed that immediate NMO ‐ IgG binding to AQP4 is not enough to affectwater channel ́s activity. However, long ‐ term exposure to NMO patient sera clearlyinduced a loss of AQP4 signal from plasma membrane, along with a significant reductionof water permeability and the capacity to regulate cell volume after an osmoticswelling (RVD), a key function of Müller cells. These data demonstrate that NMO‐ IgG targets Müller cells AQP4, affecting its expression and its function, andsubsequently cell homeostasis. Therefore, we pro ‐ pose that water permeabilityreduction after NMO ‐ IgG binding to AQP4 in Müller cells contri ‐ butes to retinalcell damage and tissue edema observed in NMO patients