The mechanisms by which the contralateral response causes the degeneration of RGCs are not completely understood. Nadal-Nicolás et al. (2015b) and Ramírez et al. (2015) proposed some theories that alone or in combination could explain this effect: (1) the direct death of retino-retinal projecting RGCs (ret-ret RGCs) (Figure 1); (2) stress signals liberated by the damaged ret-ret RGCs that cause a neurotoxic environment in the contralateral retina (Figure 1); (3) the propagation of a glial reaction through the optic chiasm (Figure 2); (4) a retrograde degeneration spreading from the deafferentated retinorecipient areas in the brain (Figure 2); and/or (5) a systemic inflammatory reaction (Figure 3).