Abstract: In the mammalian central nervous system, neuronal loss induced by injuries or in neurodegenerative diseases is often irreversible (Quigley, 2016; Gan et al., 2018). Following the disease insult, the surviving neurons may continue to lose their functionality because their axons degenerate and fail to maintain proper synaptic connections, and the underlying molecular and cellular mechanisms remain to be investigated (Raff et al., 2002; Bei et al., 2016; Quigley, 2016). Retinal ganglion cells (RGCs), for example, the neurons conveying visual information from the retina to the brain via the optic nerve, is a great model system to study the neural circuit and function because of its relatively easy accessibility and manipulation of the tissue. Optic nerve crush (ONC) injury in mice, the mechanical damage of the RGC axons at 0.5–1 mm behind the eye globe (Li et al., 1999), is a widely used model to examine the neural degeneration and axonal regeneration (Nickells et al., 2012; Quigley 2016). Since the introduction of this mouse model in late nineties, major progress has been made to characterize the axon degeneration and regeneration, especially assisted by the powerful mouse genetic tools that allow examining the molecular mechanisms underneath (Duan et al., 2015; Yi et al., 2016; Feng et al., 2017; Tran et al., 2019).