Figure 7. Key Events in Progression.
The events defining RGC degeneration in glaucoma span four critical regions: retina, optic nerve head, optic nerve and tract, and the central projection to the brain. Disease-relevant stress originating in the nerve head (marked by *) induces a program of distal axonopathy with several characteristics of chronic progression. These include failure of intra-axonal transport and subsequent loss of RGC pre-synaptic active zones and axon terminals in central projection sites, followed by degeneration of target neurons. Pathogenic features follow a distal-to-proximal progression, as in “dying back” neuropathies. In the optic nerve and tract, degeneration of the myelinated RGC axon (indicated by blue oligodendrocyte sheaths) includes features of both distal axonopathy and Wallerian degeneration, including axonal dystrophies and more acute axon disassembly beginning distal to the nerve head. Proximal degeneration is marked by elimination of synapses to RGCs, dendritic pruning and eventual somatic drop-out in the retina. In some models, retraction of the unmyelinated segment from the nerve head could arise from acute axon degeneration (see Coleman, 2005).