Abstract
Microglia are the resident phagocytic cells with various functions in the central nervous system, and the morphologies of microglia imply the different stages and functions. In optical nerve transection (ONT) model in the retina, the retrograde degeneration of retinal ganglion cells (RGCs) induces microglial activations to a unique morphology termed “rod” microglia. A few studies described the “rod” microglia in the cortex and retina; however, the function and origin of “rod” microglia are largely unknown. In the present study, we firstly studied the temporal appearance of “rod” microglia after ONT, and found the “rod” microglia emerge at approximately 7 days after ONT and peak during 14 to 21 days. Interestingly, the number of “rod” microglia remarkably decays after 6 weeks. Secondly, the “rod” microglia eliminate the degenerating RGC debris by phagocytosis. Moreover, we found the major source of “rod” microgliosis is local proliferation rather than the infiltration of peripheral monocytes/hematopoietic stem cells. We for the first time described the appearance of “rod” retinal microglia following optic nerve transection.
Highlights
Microglia are the resident phagocytic cells with various functions in the central nervous system, and the morphologies of microglia imply the different stages and functions
We examined the general patterns of microglial activation and proliferation at the ganglion cell layer (GCL)/nerve fiber layer (NFL) by whole-mount immunohistochemistry
7 days after Optic nerve transection (ONT), almost all the area of the GCL/NFL in the retinas was covered activated microglial cells, which aligned to each other and exhibited the “rod” phenotype (Fig. 1e). This phenomenon became much more evident at day 14 and day 21 after ONT, with > 80% microglia cells showing “rod” morphology (Fig. 1g,h, Fig. 2a–c), which coincident with the loss of most retinal ganglion cells (RGCs) after ONT at these time points: after proximal ONT, about 50% RGCs would be lost at day 7, which increased to 90% at day 1413
Summary
Microglia are the resident phagocytic cells with various functions in the central nervous system, and the morphologies of microglia imply the different stages and functions. In optical nerve transection (ONT) model in the retina, the retrograde degeneration of retinal ganglion cells (RGCs) induces microglial activations to a unique morphology termed “rod” microglia. Optic nerve transection (ONT) is a well-established model to induce progressive retinal ganglion cell (RGC) loss, and triggers retinal microglial activation major at the ganglion cell layer (GCL)/nerve fiber layer (NFL)[5,6]. These activated retinal microglial cells proliferate, and express progenitor cell markers such as nestin, Vimentin, and NG27,8. We examined the general patterns of microglial activation and proliferation at the GCL/NFL by whole-mount immunohistochemistry
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