Individual-Specific Modeling of Rat Optic Nerve Head Biomechanics in Glaucoma

Schwaner, Stephen A.; Perry, R. N.; Kight, Alison M.; Winder, Emily; Yang, Hongli; Morrison, John C.; Burgoyne, Claude F.; Ethier, C. Ross

doi:10.1115/1.4049157

Cited by 13 publications

(27 citation statements)

References 35 publications

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“…To be consistent with previous studies [28,29], n in these tissues was varied by ±10% about a baseline value of 0.445. The baseline values for sclera c 1 , c 3 , c 4 were near the average values retrieved in our previous inverse finite-element modelling study [11]. However, we chose to set the baseline k f value to be lower than the average for the peripapillary sclera obtained in that study.…”

Section: Sensitivity Study 241 Parametersmentioning

confidence: 77%

“…where c 1 and c 2 are the first and second Mooney-Rivlin constants and control the ground substance stiffness, K is the ground substance bulk modulus, I 1 and I 2 are the first and second invariants of the right Cauchy-Green deformation tensor and J is the determinant of the deformation gradient tensor. In all models, we set c 2 = 0 MPa and K = 1 GPa to be consistent with previous work done on the monkey as well as our own work done on the rat [11,23]. Note that since collagen fibres do not provide resistance to compressive loads, all resistance to compression is provided by the ground substance.…”

Section: Tissue Materials Modelsmentioning

confidence: 94%

“…We used the 'relative displacement' method to account for the effects of prestress in our models [17], since the measurements of ONH geometry were made from ONHs that had been perfusion-fixed at a non-zero IOP. As previously described [10,11], the pressures applied in the model (IOP, CRA blood pressure and CRV blood pressure) were ramped up in two steps. The first step brought the model to the stress state it would have experienced at perfusion fixation, i.e.…”

Section: Loads and Boundary Conditionsmentioning

confidence: 99%

“…We varied a combination of parameters dictating model geometry, tissue material properties and IOP in our sensitivity study (table 1). The baseline values for all parameters were selected either from our own data or to be consistent with values used in our previous individual-specific modelling studies, which in turn were taken from the literature [10,11]. The ranges of values were chosen to be consistent with previous sensitivity studies on human ONH biomechanics [28,29].…”

Section: Sensitivity Study 241 Parametersmentioning

confidence: 99%

“…We assumed that the perineural vascular plexus and tissue within the inferior arterial canal had the same material properties as the choroid, as they are all highly vascularized tissues. Scleral material properties were informed by our previous inverse finite-element modelling study on the rat sclera [11]. Note that only the scleral material properties were specific to the rat; all other tissue material property values from the literature were from other species.…”

Section: Sensitivity Study 241 Parametersmentioning

confidence: 99%

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Factors affecting optic nerve head biomechanics in a rat model of glaucoma

Schwaner

Feola

Ethier

2020

J. R. Soc. Interface.

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Glaucoma is the leading cause of irreversible blindness and is characterized by the death of retinal ganglion cells, which carry vision information from the retina to the brain. Although it is well accepted that biomechanics is an important part of the glaucomatous disease process, the mechanisms by which biomechanical insult, usually due to elevated intraocular pressure (IOP), leads to retinal ganglion cell death are not understood. Rat models of glaucoma afford an opportunity for learning more about these mechanisms, but the biomechanics of the rat optic nerve head (ONH), a primary region of damage in glaucoma, are only just beginning to be characterized. In a previous study, we built finite-element models with individual-specific rat ONH geometries. Here, we developed a parametrized model of the rat ONH and used it to perform a sensitivity study to determine the influence that six geometric parameters and 13 tissue material properties have on rat optic nerve biomechanical strains due to IOP elevation. Strain magnitudes and patterns in the parametrized model generally matched those from individual-specific models, suggesting that the parametrized model sufficiently approximated rat ONH anatomy. Similar to previous studies in human eyes, we found that scleral properties were highly influential: the six parameters with highest influence on optic nerve strains were optic nerve stiffness, IOP, scleral thickness, the degree of alignment of scleral collagen fibres, scleral ground substance stiffness and the scleral collagen fibre uncrimping coefficient. We conclude that a parametrized modelling strategy is an efficient approach that allows insight into rat ONH biomechanics. Further, scleral properties are important influences on rat ONH biomechanics, and additional efforts should be made to better characterize rat scleral collagen fibre organization.

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Section: Sensitivity Study 241 Parametersmentioning

confidence: 77%

Section: Tissue Materials Modelsmentioning

confidence: 94%

Section: Loads and Boundary Conditionsmentioning

confidence: 99%

Section: Sensitivity Study 241 Parametersmentioning

confidence: 99%

Section: Sensitivity Study 241 Parametersmentioning

confidence: 99%

See 3 more Smart Citations

Factors affecting optic nerve head biomechanics in a rat model of glaucoma

Schwaner

Feola

Ethier

2020

J. R. Soc. Interface.

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

Ling,

Korneva,

Quigley

et al. 2023

Biomech Model Mechanobiol

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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.

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A direct fiber approach to model sclera collagen architecture and biomechanics

Bansal

Wang

et al. 2023

Experimental Eye Research

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Individual-Specific Modeling of Rat Optic Nerve Head Biomechanics in Glaucoma

Cited by 13 publications

References 35 publications

Factors affecting optic nerve head biomechanics in a rat model of glaucoma

Factors affecting optic nerve head biomechanics in a rat model of glaucoma

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

A direct fiber approach to model sclera collagen architecture and biomechanics

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