Glaucoma: thinking in new ways-a rôle for autonomous axonal self-destruction and other compartmentalised processes?

Abstract

Glaucoma is a common neurodegenerative disease that affects retinal ganglion cells (RGCs). Substantial effort is being expended to determine how RGCs die in glaucoma. As in other neurodegenerative diseases, the majority of effort focuses on characterising apoptotic self-destruct pathways. However, apoptosis is not the only self-destruct mechanism that may be activated in neurons. It is now known that neurons have distinct classes of self-destruct programme that are spatially compartmentalised. In addition to the well-described intracellular suicide machinery in the neuronal soma, responsible for apoptosis, there is another, molecularly distinct, self-destruct programme localised in the axon. Evidence also supports the existence of compartmentalised degeneration programmes in synapses and dendrites. RGCs are no exception to this. Recent data, from in vitro studies and from an inherited mouse model of glaucoma, suggest that molecularly distinct degenerative pathways underlie the destruction of RGC somata and RGC axons. In various neurodegenerative diseases, axons, dendrites and synapses often degenerate well before the cells die, and there is increasing evidence that this is important for the production of clinical symptoms and signs. We hypothesise that such compartmentalised and autonomous programmes are of critical importance in the pathophysiology of glaucoma, and we suggest that studies of these processes are essential for a complete understanding of this complex disease.