Neuroinflammation plays a vital role in the process of a variety of retinal ganglion cells (RGCs) degenerative diseases including traumatic optic neuropathy (TON). Retinal microglial activation is believed as a harbinger of TON, and robust microglial activation can aggravate trauma-induced RGCs degeneration, which ultimately leads to RGCs loss. Toll like receptor 4 (TLR4)-triggered inflammation is of great importance in retinal inflammatory response after optic nerve injury. CD11b on macrophage and brain microglia can inhibit TLR4-triggered inflammation. However, the functional role of CD11b in retinal microglia is not well understood. Here, using an optic nerve crush model and CD11b gene deficient mice, we found that CD11b protein expression was mainly on retinal microglia, significantly increased after optic nerve injury, and still maintained at a high level till at least 28 days post crush. Compared with wild type mice, following acute optic nerve injury, CD11b deficient retinae exhibited more exacerbated microglial activation, accelerated RGCs degeneration, less growth associated protein-43 expression, as well as more proinflammatory cytokines such as interleukin-6 and tumor necrosis factor α while less anti-inflammatory factors such as arginase-1 and interleukin-10 production. We conclude that CD11b is essential in regulating retinal microglial activation and neuroinflammatory responses after acute optic nerve injury, which is critical for subsequent RGCs degeneration and loss.

中文翻译：

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整合素CD11b缺乏症加重急性视神经损伤后视网膜小胶质细胞活化和RGC变性。

神经炎症在包括损伤性视神经病变（TON）在内的多种视网膜神经节细胞（RGC）退化性疾病的过程中起着至关重要的作用。视网膜小胶质细胞活化被认为是TON的预兆，而强大的小胶质细胞活化可加剧创伤引起的RGC变性，最终导致RGC丢失。Toll样受体4（TLR4）触发的炎症在视神经损伤后的视网膜炎症反应中非常重要。巨噬细胞和脑小胶质细胞上的CD11b可以抑制TLR4触发的炎症。但是，CD11b在视网膜小胶质细胞中的功能作用尚不清楚。在这里，使用视神经挤压模型和CD11b基因缺陷型小鼠，我们发现CD11b蛋白表达主要在视网膜小胶质细胞上，在视神经损伤后明显增加，并保持高水平直到压榨后至少28天。与野生型小鼠相比，急性视神经损伤后，缺乏CD11b的视网膜表现出更严重的小胶质细胞活化，加速的RGC变性，更少的生长相关蛋白43表达，以及更多的促炎细胞因子，如白介素6和肿瘤坏死因子α，而较少的抗炎因子，例如精氨酸酶1和白介素10的产生。我们得出结论，CD11b在调节急性视神经损伤后的视网膜小胶质细胞活化和神经炎症反应中至关重要，这对于随后的RGC变性和丢失至关重要。加速了RGC的变性，减少了与生长相关的蛋白43的表达，并增加了促炎细胞因子（如白介素6和肿瘤坏死因子α），而减少了抗炎因子（如精氨酸酶1和白介素10的产生）。我们得出结论，CD11b对于调节急性视神经损伤后的视网膜小胶质细胞活化和神经炎症反应至关重要，这对于随后的RGC变性和丢失至关重要。加速了RGC的变性，减少了与生长相关的蛋白43的表达，并增加了促炎细胞因子（如白介素6和肿瘤坏死因子α），而减少了抗炎因子（如精氨酸酶1和白介素10的产生）。我们得出结论，CD11b在调节急性视神经损伤后的视网膜小胶质细胞活化和神经炎症反应中至关重要，这对于随后的RGC变性和丢失至关重要。