Abstract: Retinal ganglion cells (RGCs) are the sole output neurons of the retina that project long axons and transmit visual information to the brain. The degeneration of RGCs leads to irreversible vision loss in a variety of pathological states, including excitotoxicity, traumatic nerve injury, and glaucoma. However, an unmet clinical challenge is the lack of effective neuroprotective approaches to protect RGCs and thus preserve their function, necessitating extensive investigation of pro-survival genes in basic and translational research. Here, we first briefly describe widely used experimental models of RGC degeneration and methods for evaluating gene function in RGC survival, and then share our thoughts on the role of Ca2+/calmodulin-dependent protein kinase II (CaMKII) in regulating the survival of RGCs after excitotoxic injury.