Conclusions
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.
Methods
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.
Purpose
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.
Results
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. Conclusions: 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.