Figure 7: Molecular program of somal apoptosis and axonal degeneration after axonal injury.

Diagram of the molecules that contribute to somal and axonal degeneration in glaucoma-relevant axonal injury. Molecules in bold have been tested in ocular hypertension and deficiency of the molecules/processes in bold with red font have been shown to be protective for somal apoptosis in ocular hypertension. Question marks indicate areas currently unknown or areas where research has shown potential for bidirectional signaling. Multiple extrinsic events are thought to be important for early changes in glaucomatous neurodegeneration, but the ordering of these early changes and the possible interactions between these early changes is still poorly understood. * The role of endothelin was tested using a pan endothelin antagonist (Howell et al., 2011a). ^# Inhibition of the reduction of NAD+ has been tested in models of ocular hypertension with oral administration of nicotinamide, an NAD+ precursor, and using gene therapy to increase expression of Nmnat1 (Williams et al., 2017b). Anterograde transcriptional changes from the somal compartment are also thought to influence axonal degeneration signaling (large gray arrow, components of figure adapted from Fernandes et al., 2018).