The axoplasm of optic nerve axons moves bidirectionally at various speeds along an intra-axonal pressure gradient from the retinal ganglion cell (RGC) somata toward its synapse, and from the synapse towards the RGC somata. The axoplasmic flow of optic nerve axons is precarious even at normal intraocular pressures (IOP) as it moves from the intraocular optic nerve through the scleral lamina cribrosa to the intraorbital optic nerve. The scleral lamina cribrosa is not simply a porous region of the sclera but a specialized extracellular matrix of the central nervous system whose movement during fluctuations in IOP can affect optic nerve axoplasmic flow. The abundant optic nerve blood supply maintains adequate optic nerve head perfusion through a process of vascular autoregulation. Glaucoma is associated with reduced optic nerve axoplasmic flow and compromised optic nerve circulation such that RGC death due to glutamate excitotoxicity and neurotrophin deprivation result.