Aquaporin-4-positive neuromyelitis optica spectrum disorder linked to glial cell dysfunction

Antibodies to aquaporin-4 (AQP4) are a known pathologic marker for neuromyelitis optica spectrum disorder (NMOSD), which is classically associated with optic neuritis and transverse myelitis. In this study, the authors explored the functional and structural changes in the retina of patients with AQP4-antibody (AQP4-IgG)-positive NMOSD.

Study design

The authors compared full-field electroretinography (ERG) and OCT segmentation among 22 patients with NMOSD, 131 with multiple sclerosis (MS) and 28 healthy individuals. Fifteen patients with NMOSD were positive for AQP4-IgG antibodies (AQP4+), while the other 7 patients were AQP4-IgG negative (AQP4−).

Outcomes

The AQP4+ patients had a reduced b-wave amplitude in scotopic ERG, but not in photopic ERG, when compared with the AQP4-, MS and control groups. This reduction was mostly caused by a reduction of the slow PII component, which suggests the change arises from Müller cell dysfunction.

Patients in the AQP4+ group also had a thinner Henle fiber outer nuclear layer and inner segment layer on OCT, which was associated with the scotopic b-wave amplitude reduction. These layers correspond to the Müller cell distribution in human retinas and were shown to express AQP4 on histopathology.

Limitations

One limitation is the small sample size of NMOSD patients. While the histopathologic studies demonstrated that AQP4 expression was predominantly within Müller cells, post mortem studies in AQP4+ NMOSD patients will be required to confirm these findings.

Clinical significance

This study suggests that Müller cells are affected in eyes with AQP4+ NMOSD and therefore may play a role in the pathophysiology of AQP4 antibody-mediated disease. Future studies will be required to confirm whether ERG and retinal imaging can be used as biomarkers to diagnose AQP4+ NMOSD.