Wolf Hannah Nora, Ehinger Veronika, Guempelein Larissa, Banerjee Pratiti, Kuempfel Tania, Havla Joachim, Pauly Diana
Department of Experimental Ophthalmology, University Marburg, 35037 Marburg, Germany.
Institute of Clinical Neuroimmunology, Biomedical Center and University Hospital, Ludwig-Maximilians-Universität München, 81377 Munich, Germany.
Curr Issues Mol Biol. 2023 Sep 7;45(9):7319-7335. doi: 10.3390/cimb45090463.
Neuromyelitis optica spectrum disorders (NMOSD) are chronic inflammatory diseases of the central nervous system, characterized by autoantibodies against aquaporin-4. The symptoms primarily involve severe optic neuritis and longitudinally extensive transverse myelitis. Although the disease progression is typically relapse-dependent, recent studies revealed retinal neuroaxonal degeneration unrelated to relapse activity, potentially due to anti-aquaporin-4-positive antibodies interacting with retinal glial cells such as Müller cells. In this exploratory study, we analysed the response of mouse retinal explants to NMOSD immunoglobulins (IgG). Mouse retinal explants were treated with purified IgG from patient or control sera for one and three days. We characterized tissue response patterns through morphological changes, chemokine secretion, and complement expression. Mouse retinal explants exhibited a basic proinflammatory response ex vivo, modified by IgG addition. NMOSD IgG, unlike control IgG, increased gliosis and decreased chemokine release (CCL2, CCL3, CCL4, and CXCL-10). Complement component expression by retinal cells remained unaltered by either IgG fraction. We conclude that human NMOSD IgG can possibly bind in the mouse retina, altering the local cellular environment. This intraretinal stress may contribute to retinal degeneration independent of relapse activity in NMOSD, suggesting a primary retinopathy.
视神经脊髓炎谱系障碍（NMOSD）是中枢神经系统的慢性炎症性疾病，其特征是存在针对水通道蛋白4的自身抗体。症状主要包括严重的视神经炎和纵向广泛的横贯性脊髓炎。虽然疾病进展通常依赖于复发，但最近的研究揭示了与复发活动无关的视网膜神经轴突变性，这可能是由于抗水通道蛋白4阳性抗体与视网膜神经胶质细胞（如穆勒细胞）相互作用所致。在这项探索性研究中，我们分析了小鼠视网膜外植体对NMOSD免疫球蛋白（IgG）的反应。将小鼠视网膜外植体用来自患者或对照血清的纯化IgG处理1天和3天。我们通过形态学变化、趋化因子分泌和补体表达来表征组织反应模式。小鼠视网膜外植体在体外表现出基本的促炎反应，并因添加IgG而改变。与对照IgG不同，NMOSD IgG增加了神经胶质增生并减少了趋化因子释放（CCL2、CCL3、CCL4和CXCL-10）。视网膜细胞的补体成分表达不受任一IgG组分的影响。我们得出结论，人NMOSD IgG可能在小鼠视网膜中结合，改变局部细胞环境。这种视网膜内应激可能导致NMOSD中与复发活动无关的视网膜变性，提示存在原发性视网膜病变。
