Anti–IL-6 Receptor Antibody Suppresses Visual Dysfunction in AQP4 Peptide-Immunized Mice

Purpose: To investigate whether an anti-interleukin-6 (IL-6) receptor antibody (MR16-1) can prevent retinal and optic nerve dysfunction, as well as myelitis, in a mouse model of myelitis induced by immunization with aquaporin-4 (AQP4) peptide. Methods: Mice immunized with AQP4 peptide received MR16-1 or vehicle. Retinal function was assessed by electroretinography (ERG), including b-wave, a-wave, and positive scotopic threshold response (pSTR) amplitudes. Histologic analysis evaluated inflammatory cell infiltration and aberrant Müller cell activation (punctate pattern of glial fibrillary acidic protein staining). Blood-retinal barrier (BRB) integrity was assessed using Evans blue dye, IgG leakage, and transendothelial electrical resistance (TEER) in primary mouse retinal microvascular endothelial cells (mRMECs) exposed to mouse serum. Results: AQP4 peptide immunization led to reductions in ERG b-wave and pSTR amplitudes and increased inflammatory cell infiltration, Müller cell alteration, and retinal vascular permeability. MR16-1 treatment significantly mitigated these changes, suppressing reductions in pSTR and b-wave amplitude, preventing inflammation and aberrant Müller cell activation, and reducing vascular leakage. The improvement of a-wave amplitude was not significant. Serum from MR16-1-treated mice did not reduce mRMEC TEER, while serum from AQP4 peptide-immunized mice reduced it. Conclusions: IL-6 receptor blockade with MR16-1 has the potential to suppress AQP4 peptide immunization-related retinal and optic nerve dysfunction and pathology, likely by protecting BRB integrity and suppressing inflammation. These findings support the therapeutic potential of IL-6 inhibition in preserving visual function in neuromyelitis optica spectrum disorder (NMOSD). Translational Relevance: IL-6 receptor blockade may be a viable strategy for preventing visual impairment in patients with NMOSD.