Glaucoma and the brain: Trans-synaptic degeneration, structural change, and implications for neuroprotection

A recent hypothesis to enter the literature suggests that glaucoma is a neurodegenerative disease. The basis for this has been the finding of central nervous system changes in glaucoma patients on histology and neuroimaging. It is known that retinal ganglion cell pathology of any cause leads to anterograde and retrograde retinal ganglion cell degeneration, as well as trans-synaptic (transneuronal) anterograde degeneration. Trans-synaptic degeneration has been demonstrated in a range of optic neuropathies including optic nerve transection, optic neuritis, and hereditary optic neuropathies. More recently, similar changes have been confirmed in glaucoma patients using the neuroimaging techniques of voxel-based morphometry and diffusion tensor imaging. Some studies have reported brain changes in glaucoma outside the retino-geniculo-cortical pathway; however, these are preliminary and exploratory in nature. Further research is required to identify whether the degenerative brain changes in glaucoma are entirely secondary to the optic neuropathy or whether there is additional primary central nervous system pathology. This has critical implications for neuroprotective and regenerative treatment strategies and our basic understanding of glaucoma.