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Integrin CD11b Deficiency Aggravates Retinal Microglial Activation and RGCs Degeneration After Acute Optic Nerve Injury

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Abstract

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.

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Acknowledgements

We thank Prof. Yuan-Guo Zhou from Army Medical Center of PLA and Prof. Feng Mei from Army Medical University for project consultation and kind review of the manuscript, and thank Prof. Bo Peng from ShenZhen Institutes of Advanced Technology, Chinese Academy of Sciences for his technical support. This work was supported by the Funds of National Natural Science Foundation of China (Nos. 81570840 and 81371006), Basic Research and Frontier Fund of Chongqing (cstc2019jcyj-msxmX0010) and Research Foundation of Dept. Ophthalmology in Daping Hospital, AMU (No. 9-2543).

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  1. Xiao-Feng Cai, Sen Lin and Zhao Geng contributed equally to this work as co-first authors.

Authors and Affiliations

  1. Department of Ophthalmology, Research Institute of Surgery & Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, 400042, People’s Republic of China

    Xiao-Feng Cai, Sen Lin, Zhao Geng, Lin-Lin Luo, Yun-Jia Liu, Zhou Zhang, Wen-Yi Liu, Xi Chen, Xue Li & Jian Ye

  2. State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery & Daping Hospital, Army Medical Center of PLA, Army Medical University, Chongqing, 400042, People’s Republic of China

    Jun Yan

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  1. Xiao-Feng Cai
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Cai, XF., Lin, S., Geng, Z. et al. Integrin CD11b Deficiency Aggravates Retinal Microglial Activation and RGCs Degeneration After Acute Optic Nerve Injury. Neurochem Res 45, 1072–1085 (2020). https://doi.org/10.1007/s11064-020-02984-6

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