The Brain in Glaucomatous Optic Neuropathy: Evidence for Trophic-Factor Mediated Self-Repair

As in other age-related neurodegenerative diseases, progression of neurodegeneration in glaucoma involves early axonopathy. In glaucoma, this is marked by degradation of active transport along retinal ganglion cell (RGC) axons stretching from the retina to the brain. In experimental systems, transport degradation fails first in the most distal site in the optic projection, the superior colliculus of the midbrain. Even as degradation progresses from one retinotopic sector to the next, important structures in the affected sectors persist, including RGC synapses to SC neurons. This structural persistence defines a therapeutic window of opportunity and is accompanied by focally increased brain-derived neurotrophic factor (BDNF) in hypertrophic SC astrocyte glia. Thus, central brain structures in glaucoma may respond to disease-relevant stress by induction of mechanisms useful for maintaining retinal signals.