Glaucoma is characterized by a progressive damage of the retina and the optic nerve. Despite a huge research interest, the exact pathomechanisms are still unknown. In the experimental autoimmune glaucoma model, rats develop glaucoma-like damage of the retina and the optic nerve after immunization with an optic nerve antigen homogenate (ONA). An early activation of the complement system, even before optic nerve degeneration, was reported in this model. Here, we investigated the effects of a monoclonal antibody against complement factor C5 on optic nerves. Rats were immunized with ONA and compared to controls. In one eye of some ONA animals, the antibody against C5 was intravitreally injected (15 μmol: ONA + C5-I or 25 μmol: ONA + C5-II) before immunization and then every 2 weeks. After 6 weeks, optic nerves were processed for histology (n = 6/group). These analyses demonstrated that the intravitreal therapy reduced the depositions of the membrane attack complex compared to ONA animals (ONA + C5-I: p = 0.005; ONA + C5-II: p = 0.002). Cellular infiltration was significantly reduced in the ONA + C5-I group (p = 0.003), but not in ONA + C5-II tissues (p = 0.41). Furthermore, SMI-32 staining revealed that neurofilament was preserved in both treatment groups compared to ONA optic nerves (both p = 0.002). A decreased amount of microglia was found in treated animals in comparison to the ONA group (ONA + C5-I: p = 0.03; ONA + C5-II: p = 0.009). We observed, for the first time, that a complement system inhibition could prevent optic nerve damage in an autoimmune glaucoma model. Therefore, complement inhibition could serve as a new therapeutic tool for glaucoma.

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实验性青光眼补体抑制保护视神经结构

青光眼的特征是视网膜和视神经的进行性损伤。尽管有巨大的研究兴趣，但确切的发病机制仍然未知。在实验性自身免疫性青光眼模型中，大鼠在用视神经抗原匀浆 (ONA) 免疫后出现视网膜和视神经的青光眼样损伤。在该模型中报告了补体系统的早期激活，甚至在视神经退化之前。在这里，我们研究了针对补体因子 C5 的单克隆抗体对视神经的影响。用ONA免疫大鼠并与对照进行比较。在一些 ONA 动物的一只眼睛中，在免疫前玻璃体内注射抗 C5 抗体（15 μmol：ONA + C5-I 或 25 μmol：ONA + C5-II），然后每 2 周注射一次。6周后，对视神经进行组织学处理（n = 6/组）。这些分析表明，与 ONA 动物相比，玻璃体内治疗减少了膜攻击复合物的沉积（ONA + C5-I：p = 0.005；ONA + C5-II：p = 0.002）。ONA + C5-I 组的细胞浸润显着减少 (p = 0.003)，但在 ONA + C5-II 组织中没有 (p = 0.41)。此外，SMI-32 染色显示，与 ONA 视神经相比，两个治疗组都保留了神经丝（均 p = 0.002）。与 ONA 组相比，在接受治疗的动物中发现小胶质细胞数量减少（ONA + C5-I：p = 0.03；ONA + C5-II：p = 0.009）。我们首次观察到补体系统抑制可以预防自身免疫性青光眼模型中的视神经损伤。所以，