The molecular biology of retinal ganglion cell death: caveats and controversies.

Understanding the molecular pathways activated in dying retinal ganglion cells may lead to the development of therapies aimed at blocking the cell death process. As we learn more about ganglion cell death, it is becoming clear that several new hurdles must be overcome before preventing this process can be a realistic therapy. This review details three caveats about retinal ganglion cell death that should be considered. The first caveat centers on a critical step in the cell death pathway involving mitochondria. Blocking biochemical events after mitochondrial dysfunction, such as the caspase cascade, may provide only a transient effect on survival, since the cell has already sustained lethal damage. The second caveat is that blocking one cell death pathway may be ineffective because alternate pathways can become active. This caveat seems to be particularly relevant in neurons exposed to excitotoxic insults. The third caveat is that although it is possible to block cell death, this does not guarantee that the cell will be able to function normally. Consequently, it may be important to provide additional treatment to restore normal cell function in conjunction with therapies aimed at preventing their death.