Neuromyelitis optica/spectrum disorder (NMO/SD) is a severe, inflammatory disease of the central nervous system (CNS). In the majority of patients, it is associated with the presence of pathogenic serum
autoantibodies (the so-called NMO-IgGs) directed against the
water channel aquaporin 4 (AQP4), and with the formation of large, astrocyte-destructive lesions in spinal cord and optic nerves. A large number of recent studies using optical coherence tomography (OCT) demonstrated that damage to optic nerves in NMO/SD is also associated with
retinal injury, as evidenced by
retinal nerve fiber layer (RNFL) thinning and microcystic inner nuclear layer abnormalities. These studies concluded that
retinal injury in NMO/SD patients results from secondary neurodegeneration triggered by
optic neuritis.However, the eye also contains cells expressing AQP4, i.e., Müller cells and astrocytes in the retina, epithelial cells of the ciliary body, and epithelial cells of the iris, which raised the question whether the eye can also be a primary target in NMO/SD. Here, we addressed this point in experimental NMO/SD (ENMO) induced in Lewis rat by transfer of AQP4268-285-specific T cells and NMO-
IgG.We show that these animals show
retinitis and subsequent dysfunction/damage of
retinal axons and neurons, and that this pathology occurs independently of the action of NMO-
IgG. We further show that in the retinae of ENMO animals Müller cell side branches lose AQP4 reactivity, while
retinal astrocytes and Müller cell processes in the RNFL/ganglionic cell layers are spared. These changes only occur in the presence of both AQP4268-285-specific T cells and NMO-
IgG.Cumulatively, our data show that damage to
retinal cells can be a primary event in NMO/SD.