The molecular mechanism of axonal degeneration in the optic nerve remains unclear. The optic nerve contains axons and glia such as oligodendrocytes, astrocytes, as well as microglia. Tumor necrosis factor (TNF) has been implicated in the pathogenesis of glaucomatous optic neuropathy (GON). A TNF-induced optic nerve degeneration model demonstrated primary axonal degeneration and subsequent retrograde loss of retinal ganglion cell bodies. In this review, we address the molecular mechanism of axonal degeneration from the viewpoint of the axons and surrounding glial cells. Brain-derived neurotrophic factor and the amyloidogenic pathway may play important roles in glial events, while nicotinamide mononucleotide adenylyltransferase 1 and thioredoxin 1 may play important roles within axons. Understanding the molecular mechanisms of axonal degeneration in the optic nerve will open a new avenue for treatment of GON by introducing the novel concept of "axoprotectant".
Nippon Ganka Gakkai Zasshi (J Jpn Ophthalmol Soc) 117: 878-885, 2013.