Computational study of the mechanical behavior of the astrocyte network and axonal compartments in the mouse optic nerve head

Abstract

Glaucoma is a blinding disease characterized by the degeneration of the retinal ganglion cell (RGC) axons at the optic nerve head (ONH). A major risk factor for glaucoma is the intraocular pressure (IOP). However, it is currently impossible to measure the IOP-induced mechanical responses in the axons of the ONH. The objective of this study was to develop a computational model to estimate the IOP-induced strains and stresses in the axonal compartments in the mouse astrocytic lamina (AL) of the ONH, and to investigate the effect of the structural features on the mechanical behavior. We developed experimentally-informed finite element (FE) models of six mouse AL to investigate the effect of structure on the stress and strain response of the astrocyte network and axonal compartments to pressure elevation. The Computational Study of the Mouse ONH specimen-specific geometries of the FE models were reconstructed from confocal fluorescent images of cryosections of the mouse AL acquired in a previous study that measured the structural features of the astrocytic processes and axonal compartments. The displacement fields obtained from digital volume correlation in prior inflation tests of the mouse AL were used to determine the in-plane boundary conditions of the FE models. We applied a machine learning algorithm, Gaussian process regression, to analyze the effects of the structural features on the strains and stresses simulated for each axonal compartment. The axonal compartments experienced, on average, 5 times higher maximum principal strain but 1800 times lower maximum principal stress compared to that experienced by the astrocyte processes. The mechanical responses in the axonal compartments were most sensitive to variations in the area and orientation of the axonal compartments. Larger axonal compartments that were more vertically aligned, closer to the AL center, and with lower local actin area fraction had higher strains. Understanding the factors affecting the deformation and stress state in the axonal compartments will provide insights into mechanisms of glaucomatous axonal damage.