The proposed involvement of CNTF, JAK/STAT, and MAPK signaling in gliosis and neural regeneration by Müller glia in mammalian retina. Retinal injury (lightning bolt) kills retinal cells (gray cells) and stimulates release of growth factors, including CNTF, resulting in limited cell division of Müller glia (MG). In the absence of exogenous growth factors, increased JAK/STAT signaling (lower arrows) in activated MG promotes gliosis (bright green), resulting in glial scars, but neurons are not regenerated. Activation of MAPK and JAK/STAT signaling by exogenous factors, including EGF, FGF2, and insulin (upper arrows), produces proliferative progenitors (light green), which can regenerate some retinal neurons (in gray shaded oval), such as amacrine cells [62
] and photoreceptors [63
]. Some undifferentiated progenitor cells (light green) persist following resolution of the regenerative response. Even with exogenous factor stimulation, mammalian retinas fail to restore all lost cells.