Abstract
Neuromyelitis optica (NMO) is an autoimmune inflammatory demyelinating disease that mainly affects the spinal cord and optic nerve, causing blindness and paralysis in some individuals. Moreover, NMO may cause secondary complement-dependent cytotoxicity (CDC), leading to oligodendrocyte and neuronal damage. In this study, a rodent NMO model, showing typical NMO pathogenesis, was induced with NMO-IgG from patient serum and human complement. We then tested whether the combination of C16, an αvβ3 integrin-binding peptide, and angiopoietin-1 (Ang1), a member of the endothelial growth factor family, could alleviate NMO in the model. Our results demonstrated that this combination therapy significantly decreased disease severity, inflammatory cell infiltration, secondary demyelination, and axonal loss, thus reducing neural death. In conclusion, our study suggests a possible treatment that can relieve progressive blindness and paralysis in an animal model of NMO through improvement of the inflammatory milieu.
Highlights
Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that selectively targets the optic nerves and spinal cord, leading to blindness and paralysis [1]
Since NMO patients often present demyelinating lesions in the central nervous system (CNS), it has long been considered a variant of multiple sclerosis (MS); recent data suggest that its pathogenesis may be different [2]
NMO-IgG selectively binds to the water channel aquaporin-4 (AQP4), which is densely expressed in astrocytic foot processes at the blood-brain barrier (BBB), destroying the integrity of the BBB
Summary
Neuromyelitis optica (NMO) is an autoimmune inflammatory disease that selectively targets the optic nerves and spinal cord, leading to blindness and paralysis [1]. Since NMO patients often present demyelinating lesions in the central nervous system (CNS), it has long been considered a variant of multiple sclerosis (MS); recent data suggest that its pathogenesis may be different [2]. The immunopathology of NMO includes restricted demyelination and inflammation of the optic nerves and several spinal segments [3]. Pathological characteristics of NMO include loss of AQP4 and glial fibrillary acidic protein (GFAP) and granulocyte and macrophage infiltration, as well as demyelination and axonal injury mainly in the spinal cord and optic nerves of NMO patients [4]. The pathogenicity of NMO-IgG (anti-AQP4 autoantibodies) and human complement has been investigated, contributing to the initial NMO model [4,5,6,7,8]
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