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

Area of Science:

• Neuroscience
• Immunology
• Ophthalmology

Background:

• Neuromyelitis optica spectrum disorder (NMOSD) involves inflammation targeting the optic nerve and spinal cord.
• Aquaporin-4 (AQP4) peptide immunization in mice serves as a model for NMOSD-related pathology.
• Interleukin-6 (IL-6) is implicated in neuroinflammation and autoimmune diseases.

Purpose of the Study:

• To investigate the efficacy of an anti-IL-6 receptor antibody (MR16-1) in preventing visual pathway dysfunction.
• To assess the impact of MR16-1 on retinal and optic nerve pathology in an AQP4 peptide-induced mouse model.
• To determine if IL-6 receptor blockade can mitigate myelitis and associated visual impairments.

Main Methods:

• Mice were immunized with AQP4 peptide and treated with MR16-1 or vehicle.
• Retinal function was evaluated using electroretinography (ERG).
• Histology assessed inflammation and Müller cell activation; blood-retinal barrier (BRB) integrity was measured.

Main Results:

• AQP4 immunization caused reduced ERG amplitudes, inflammation, and BRB leakage.
• MR16-1 treatment significantly ameliorated these deficits, preserving retinal function and BRB integrity.
• MR16-1 suppressed inflammation and aberrant Müller cell activation, unlike the control group.

Conclusions:

• IL-6 receptor blockade with MR16-1 shows potential in preventing AQP4 peptide-induced visual dysfunction.
• MR16-1 likely protects BRB integrity and reduces inflammation, supporting its therapeutic role in NMOSD.
• Targeting IL-6 signaling may be a promising strategy for preserving vision in NMOSD patients.