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Therapeutic strategies for neuromyelitis optica spectrum disorder target pathogenic mechanisms of the disease and aim to restore the blood–brain barrier and enhance immune tolerance.

Potential therapeutic strategies for neuromyelitis optica spectrum disorder (NMOSD) are based on targeting the B cell complement cascade system, and IL-6R. These strategies include restoration of the blood–brain barrier (BBB) and enhanced immune tolerance. The study findings are published in the International Journal of Molecular Sciences.

Serum Antibodies in NMOSD

The clinical diagnosis of this neuroinflammatory disorder is based on the presence of serum NMO-IgG (AQP4-IgG) antibodies in the serum, along with the symptoms included in the International Panel for NMO Diagnosis. The serum antibodies are important biological markers for predicting the prognosis and relapse of the disease.

Pathogenesis of NMOSD

AQP4 stabilizes extracellular osmolality in neuronal activity. In the BBB, AQP4 is responsible for energy, glutamate, and metabolic load homeostasis. There is a loss of expression of AQP4 in astrocytes in NMOSD along with the activation of the complement system, myelin loss, thickened vascular hyalinization, eosinophil degranulation, and infiltration of macrophages, microglia, and neutrophils. AQP4-IgG leads to Muller cell dysfunction resulting in retinal pathology.

Cytotoxic Pathway Mediates Astrocyte Injury in NMOSD

Cellular cytotoxicity in NMOSD promotes astrocyte injury. Antibody-dependent cellular toxicity (ADCC) mediates the activation of natural killer (NK) cells and macrophages. In contrast, complement-dependent cytotoxicity (CDC) mediates cell damage by stimulating the classic complement pathway, which yields the membrane attack complex (MAC). NMOSD is also characterized by peripheral autoimmune dysregulation, which causes central nervous system (CNS) inflammation by disrupting tight junctions in the BBB. These mechanisms highlight the therapeutic potential of restoring immune tolerance in the body.

Biomarkers and Optical Coherence Tomography Angiography in the Evaluation of NMOSD

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The standardized biomarker for assessing the pathophysiology and clinical course of this disease is (optical coherence tomography) OCT; however, surrogate serum markers, including neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP), can be used as well. OCT has been used to identify macular and optic nerve structures in diagnosing NMOSD. OCT angiography is potentially useful for the evaluation of microvascular impairment and in the monitoring of NMOSD patients.

Animal Models and Their Limitations in NMOSD

Animal models facilitate studying of NMOSD owing to their ability to produce human NMO-like lesions. Their limitations include greater complexity of anatomical structures and relatively variable immune responses in humans.

The restoration of the BBB and enhanced immune tolerance are potential strategies for the treatment of NMOSD. The development of animal models will help improve the understanding of pathological and therapeutic mechanisms in this disease.


Huang, T.-L., Wang, J.-K., Chang, P.-Y., Hsu, Y.-R., Lin, C.-H., Lin, K.-H., & Tsai, R.-K. (2022). Neuromyelitis Optica Spectrum Disorder: From Basic Research to Clinical Perspectives. International Journal of Molecular Sciences, 23(14), 7908. https://www.mdpi.com/1422-0067/23/14/7908