As illustrated by the blue triangles at the bottom, different states of the enzymatic or catalytic activities of caspase-8 are critical for the outcome: (A) Enzymatic activity of caspase-8 induces apoptosis (as in RGCs), (B) catalytic activity (in the absence of full proteolytic cleavage) signals towards cell survival (as in astroglia, or z-IETD-fmk-treated RGCs) and (C) no caspase-8 activity induces necroptosis (as in caspase-8-deleted astroglia). Thus, caspase-8 deletion in astroglia changes the state from “B to C”, while the inhibition of caspase-8 cleavage shifts the signal from “A to B” in RGCs.