Gadolinium chloride protects neurons by regulating the activation of microglia in the model of optic nerve crush.

The pathological basis of optic nerve crush (ONC) is the apoptosis of retinal ganglion cells (RGCs), which leads to an irreversible impairment of visual function. When stimulated by external stimuli, microglia polarize into different types and play different roles in repairing retinal injury. In this study, gadolinium chloride (GdCl3) could inhibit the excessive proliferation and activation of microglia in the retina after ONC and significantly inhibited the morphological changes of microglia in the ganglion cell layer (GCL) and inner plexiform layer (IPL). In the early stage of optic nerve injury, blood-derived immune cells did not play an essential role in retinal repair. In addition, transcriptome analysis showed that GdCl3 inhibited the expression of microglia proliferation-related factors and regulated signaling pathways related to skeletonization and inflammation. After GdCl3 treatment, M1 markers were significantly down-regulated, while M2 markers were increased. In conclusion, this study demonstrated that GdCl3 could regulate the distribution and morphological change of the retinal microglia and protect the ganglion cells by eliminating M1 microglia selectively, which provided a theoretical basis for further localizing different types of microglia in retina related diseases.