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

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

Paris

Congreso; Congress of the International Society for Neurochemestry (ISN 2017); 2017

Neuromyelitis optica immunoglobulin G targets AQP4expressed in retinal M?uller cells affecting cell volumehomeostasisC. Capurro1, V. Netti1, J. Fern!andez1, G. Di Giusto1, V. Rivarola1, P.Ford1, L. Melamud21Universidad de Buenos Aires, Departamento de Fisiolog"ıa yBiof"ısica, Buenos Aires, Argentina2Hospital de Agudos J.M. Ramos Mej"ıa, Centro Universitario deNeurolog"ıa, Buenos Aires, ArgentinaThe current study evaluates if the water channel AQP4, highlyexpressed in M?uller cells in the retina, is a pathogenic ocular targetof specific serum immunoglobulin G autoantibody (NMO-IgG)produced in patients with Neuromyelitis Optica. Particularly weinvestigated the consequences of NMO-IgG binding to AQP4 onplasma membrane water permeability and cell volume homeostasis.Studies were performed in a human retinal M?uller cell line (MIOM1),a good model that maintains important functional characteristicsof M?uller cells. To avoid or to facilitate AQP4 downregulation,cells were exposed to inactivated control or positiveNMO-IgG sera in two different situations (1 hr at 4°C or 12 hr at37°C). AQP4 expression was detected by immunofluorescencestudies using a polyclonal anti-AQP4 antibody and the waterpermeability coefficient and cell volume regulation capacity wereevaluated by fluorescence videomicroscopy. Our results showed thatimmediate NMO-IgG binding to AQP4 is not enough to affect waterchannel0s activity. However, long-term exposure to NMO patientsera clearly induced a loss of AQP4 signal from plasma membrane,along with a significant reduction of water permeability and thecapacity to regulate cell volume after an osmotic swelling (RVD), akey function of M?uller cells. These data demonstrate that NMO-IgGtargets M?uller cells AQP4, affecting its expression and its function,and subsequently cell homeostasis. Therefore, we propose that waterpermeability reduction after NMO-IgG binding to AQP4 in M?ullercells contributes to retinal cell damage and tissue edema observed inNMO patients.