A biomechanical paradigm for axonal insult within the optic nerve head in aging and glaucoma

This article is dedicated to Rosario Hernandez for her warm support of my own work and her genuine enthusiasm for the work of her colleagues throughout her career. I first met Rosario as a research fellow in Harry Quigley’s laboratory between 1991 and 1993. Along with Harry, John Morrison, Elaine Johnson, Abe Clark, Colm O’Brien and many others, Rosario’s work has provided lamina cribrosa astrocyte cellular mechanisms that are biomechanically plausible and in so doing provided credibility to early notions of the optic nerve head (ONH) as a biomechanical structure.We owe a large intellectual debt to Rosario for her dogged persistence in the characterization of the ONH astrocyte and lamina cribrosacyte in age and disease. Two questions run through her work and remain of central importance today. First, how do astrocytes respond to and alter the biomechanical environment of the ONH and the physiologic stresses created therein? Second, how do these physiologic demands on the astrocyte influence their ability to deliver the support to retinal ganglion cell axon transport and flow against the translaminar pressure gradient?The purpose of this article is to summarize what is known about the biomechanical determinants of retinal ganglion cell axon physiology within the ONH in the optic neuropathy of aging and Glaucoma. My goal is to provide a biomechanical framework for this discussion. This framework assumes that the ONH astrocytes and glia fundamentally support and influence both the lamina cribrosa extracellular matrix and retinal ganglion cell axon physiology. Rosario Hernandez was one of the first investigators to recognize the implications of this unique circumstance. Many of the ideas contained herein have been initially presented within or derived from her work (Hernandez, M.R., 2000. The optic nerve head in glaucoma: role of astrocytes in tissue remodeling. Prog Retin Eye Res. 19, 297–321.; Hernandez, M.R., Pena, J.D., 1997. The optic nerve head in glaucomatous optic neuropathy. Arch Ophthalmol. 115, 389–395.).

► Glaucoma, cupping and axonal insult within the optic nerve head (ONH).
► The Biomechanical Paradigm of Glaucomatous damage to the ONH.
► ONH Connective Tissue Biomechanics and the Translaminar Pressure Gradient.
► Retinal Ganglion Cell (RGC) Axon Transport within the ONH.
► The mechanisms of RGC axon insult in glaucoma are likely to be multifactorial and different by regions of the ONH and stage of the disease.
► Future Directions – Important Studies.