Gaps in the fundamental knowledge of neurotrophic factors (NTFs) in the adult visual system. (A,B) Many fundamental questions regarding the NTF cocktail essential for retinal ganglion cell (RGC) survival remain unanswered. Precisely which NTFs are involved? Is the interplay between two or more NTFs a bare necessity? If so, what is the ideal ratio of each NTF in the cocktail? Do vital NTFs originate from local sources or from target areas, or both; and from which specific cell type—i.e., neurons and/or glial cells? (C,D) Also on cellular level, a number of research questions are yet to be unraveled regarding the NTF mechanism of action. How do NTFs function upon receptor binding? What is the complete array of involved signaling molecules and pathways? (A,C versus B,D) All of the abovementioned parameters might differ depending on the site of NTF presentation: at the cell soma (C) or at the presynaptic terminals (B,D). For example, recruitment of downstream signaling molecules varies upon the location where the signaling machinery is switched on: the cell soma for retinal NTFs (C) versus the distal axon for target-derived NTFs (D).