It is known that intravitreally injected N-methyl-d-aspartate (NMDA) leads to fast retina and optic nerve degeneration and can directly activate microglia. Here, we analyzed the relevance for microglia related degenerating factors, the proteins of the complement system, at a late stage in the NMDA damage model. Therefore, different doses of NMDA (0 (PBS), 20, 40, 80 nmol) were intravitreally injected in rat eyes. Proliferative and activated microglia/macrophages (MG/Mϕ) were found in retina and optic nerve 2 weeks after NMDA injection. All three complement pathway proteins were activated in retinas after 40 and 80 nmol NMDA treatment. 80 nmol NMDA injection also lead to more numerous depositions of complement factors C3 and membrane attack complex (MAC) in retina and MAC in optic nerve. Additionally, more MAC+ depositions were detected in optic nerves of the 40 nmol NMDA group. In this NMDA model, the retina is first affected followed by optic nerve damage. However, we found initiating complement processes in the retina, while more deposits of the terminal complex were present 2 weeks after NMDA injection in the optic nerve. The complement system can be activated in waves and possibly a second wave is still on-going in the retina, while the first activation wave is in the final phase in the optic nerve. Only the damaged tissues showed microglia activation as well as proliferation and an increase of complement proteins. Interestingly, the microglia/macrophages (MG/Mϕ) in this model were closely connected with the inductors of the classical and lectin pathway, but not with the alternative pathway. However, all three initiating complement pathways were upregulated in the retina. The alternative pathway seems to be triggered by other mechanisms in this NMDA model. Our study showed an ongoing interaction of microglia and complement proteins in a late stage of a degenerative process.

中文翻译：

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NMDA损伤模型中视网膜和视神经中补体系统和小胶质细胞活化的相互作用。

众所周知，玻璃体内注射N-甲基-d-天冬氨酸（NMDA）会导致视网膜和视神经快速变性，并可以直接激活小胶质细胞。在这里，我们分析了NMDA损伤模型后期与小胶质细胞相关的退化因子，补体系统蛋白的相关性。因此，在大鼠眼内玻璃体内注射了不同剂量的NMDA（0（PBS），20、40、80nmol）。NMDA注射后2周，在视网膜和视神经中发现了增生和活化的小胶质细胞/巨噬细胞（MG / Mϕ）。在40和80 nmol NMDA处理后，视网膜中的所有三种补体途径蛋白均被激活。80 nmol NMDA注射还会导致视网膜中的补体因子C3和膜攻击复合物（MAC）以及视神经中的MAC沉积更多。另外，在40 nmol NMDA组的视神经中检测到更多的MAC +沉积。在这种NMDA模型中，首先会影响视网膜，然后是视神经损伤。然而，我们发现在视网膜中补体过程开始，而在视神经中注射NMDA后2周，终末复合物出现更多沉积。补体系统可以波激活，而第二波可能仍在视网膜中进行，而第一个激活波处于视神经的末期。仅受损组织显示小胶质细胞活化，增殖和补体蛋白增加。有趣的是，该模型中的小胶质细胞/巨噬细胞（MG / Mϕ）与经典途径和凝集素途径的诱导剂紧密相连，但与替代途径没有紧密联系。然而，视网膜中所有三个起始补体途径均被上调。替代途径似乎是由该NMDA模型中的其他机制触发的。我们的研究表明，在退化过程的后期，小胶质细胞和补体蛋白之间正在进行相互作用。