Department of Ophthalmology, Daping Hospital, Army Medical Center of PLA, Third Military Medical University (Army Medical University), Chongqing, China.
Department of Neurology, Xinqiao Hospital and The Second Affiliated Hospital, Third Military Medical University (Army Medical University), Chongqing, China.
Invest Ophthalmol Vis Sci. 2023 May 1;64(5):7. doi: 10.1167/iovs.64.5.7.
Microglial clearance of axonal debris is an essential response for management of traumatic optic neuropathy. Inadequate removal of axonal debris leads to increased inflammation and axonal degeneration after traumatic optic neuropathy. The present study investigated the role of CD11b (Itgam) in axonal debris clearance and axonal degeneration.
Western blot and immunofluorescence were used to detect CD11b expression in the mouse optic nerve crush (ONC) model. Bioinformatics analysis predicted the possible role of CD11b. Cholera toxin subunit B (CTB) and zymosan were used to assay phagocytosis by microglia in vivo and in vitro, respectively. CTB was also used to label functionally intact axons after ONC.
CD11b is abundantly expressed after ONC and participates in phagocytosis. Microglia from Itgam-/- mice exhibited more significant phagocytosis of axonal debris than wild-type microglia. In vitro experiments confirmed that the CD11b gene defect in M2 microglia leads to increased insulin-like growth factor-1 secretion and thus promotes phagocytosis. Lastly, following ONC, Itgam-/- mice exhibited elevated expression of neurofilament heavy peptide and Tuj1, along with more intact CTB-labeled axons when compared with wild-type mice. Moreover, the inhibition of insulin-like growth factor-1 decreased CTB labeling in Itgam-/- mice after injury.
CD11b limits microglial phagocytosis of axonal debris in traumatic optic neuropathy, as demonstrated by increased phagocytosis with CD11b knockout. The inhibition of CD11b activity may be a novel approach to promote central nerve repair.
小胶质细胞清除轴突碎片是外伤性视神经病变管理的必要反应。轴突碎片清除不足会导致外伤性视神经病变后炎症反应和轴突变性增加。本研究探讨了 CD11b（Itgam）在外周神经损伤后清除轴突碎片和轴突变性中的作用。
采用 Western blot 和免疫荧光技术检测小鼠视神经挤压（ONC）模型中 CD11b 的表达。生物信息学分析预测 CD11b 的可能作用。霍乱毒素亚单位 B（CTB）和酵母聚糖分别用于检测小胶质细胞体内和体外的吞噬作用。CTB 也用于标记 ONC 后功能完整的轴突。
ONC 后 CD11b 表达丰富，并参与吞噬作用。Itgam-/- 小鼠的小胶质细胞比野生型小胶质细胞表现出更强的吞噬轴突碎片的能力。体外实验证实，M2 小胶质细胞中 CD11b 基因缺陷导致胰岛素样生长因子-1 分泌增加，从而促进吞噬作用。最后，与野生型小鼠相比，ONC 后 Itgam-/- 小鼠的神经丝重肽和 Tuj1 表达升高，CTB 标记的轴突更完整。此外，胰岛素样生长因子-1 的抑制减少了 Itgam-/- 小鼠损伤后 CTB 的标记。
CD11b 通过 CD11b 基因敲除导致吞噬作用增加，从而限制外伤性视神经病变中小胶质细胞对轴突碎片的吞噬作用。抑制 CD11b 活性可能是促进中枢神经修复的一种新方法。
