Finite element modeling of optic nerve head biomechanics in a rat model of glaucoma

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Schwaner, Stephen Andrew
Ethier, C. Ross
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Glaucoma is the leading cause of irreversible blindness and is characterized by the dysfunction of retinal ganglion cells (RGC), the cells that send vision information from the retina to the brain. All current therapies focus on lowering intraocular pressure (IOP), a causative risk factor in the disease. However, they are not always effective. Although it is well-accepted that elevated IOP-induced biomechanical insult to the optic nerve head (ONH), the region in the posterior eye where RGC axons exit, is key to glaucoma pathophysiology, the mechanisms by which biomechanical insult leads to RGC death are unknown. Rat glaucoma models present an opportunity for understanding glaucoma biomechanics and are widely used in the field. However, rat ONH biomechanics have not been characterized and rat ONH anatomy differs substantially from the human. Therefore, the purpose of this thesis was to provide the first characterization of rat ONH biomechanics to the glaucoma field. To this end, we completed three specific aims. First, we used inverse modeling combined with whole-eye inflation testing to extract material properties from the rat sclera. Second, we conducted a sensitivity study to investigate the effects of anatomical and material property variation on rat ONH strains using a parameterized finite element model of the rat ONH. Lastly, we developed a methodology for building rat ONH FE models with individual-specific geometry and simulated the effects of elevated IOP. Key results include the finding that the patterns of strain in the rat ONH are less symmetric than those in the human, and the highest strains occur in the inferior nerve. In all three aims, the results emphasized the importance of collagen fiber organization on optic nerve strains. Lastly, the patterns and magnitude of optic nerve strain in the parameterized model showed good concordance with those observed in the individual-specific models, suggesting that the higher throughput parameterized models may be able to replace individual-specific models of the rat ONH moving forward. The results from this work can serve to inform future modeling studies on rat ONH biomechanics and provide context for interpreting rat glaucoma studies with the goal of learning more about the link between biomechanical insult and RGC pathophysiology in glaucoma.
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