We established a new AQP4-associated ON model that reproduces the histological characteristics of ON in NMO patients, including loss of AQP4 and GFAP, immune cell infiltration, extensive damage of the RGC axons, and impairment of visual function, using a high-affinity anti-AQP4 monoclonal antibody. This evidence concerns the gene AQP4 and neuromyelitis optica.