Aquaporin 4-specific T cells and NMO-IgG cause primary retinal damage in experimental NMO/SD

Bleranda Zeka, Maria Hastermann, Nathalie Kaufmann, Kathrin Schanda, Marko Pende, Tatsuro Misu, Paulus Rommer, Kazuo Fujihara, Ichiro Nakashima, Charlotte Dahle, Fritz Leutmezer, Markus Reindl, Hans Lassmann, Monika Bradl

研究成果: Article査読

28 被引用数 (Scopus)

抄録

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.

本文言語English
論文番号82
ジャーナルActa Neuropathologica Communications
4
1
DOI
出版ステータスPublished - 2016

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

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