Intracellular flow in optic nerve axons: a mechanism for cell death in glaucoma

PURPOSE. In glaucoma, elevated intraocular pressure causes a progressive loss of retinal ganglion cells and results in optic neuropathy. The authors propose a potential mechanism for cell death, whereby elevated intraocular pressure causes fluid to permeate axonal membranes, creating a passive intracellular fluid flow within the axons. It is hypothesized that this intracellular flow locally depletes the adenosine triphosphate (ATP) concentration, disrupting axonal transport and leading to cell death. METHODS. A mathematical model was developed that takes into account the biomechanical principles underpinning the proposed hypothesis, and was solved to determine the implications of the mechanism. RESULTS. The model suggests that the raised intraocular pressures present in glaucoma are adequate to produce significant intracellular fluid flow. In the periphery of the optic nerve head, this flow may be sufficient to disrupt the diffusion of ATP and hence interrupt active axonal transport. CONCLUSIONS. The mathematical model demonstrates that it is physically plausible that a passive intracellular fluid flow could significantly contribute to the pathophysiology of the retinal ganglion cell axon in glaucoma. (Invest Ophthalmol Vis Sci. 2009; 50: 3750-3758) DOI: 10.1167/iovs.08-2396