BioE PhD Defense Presentation- Stephen Schwaner

Advisor:

C. Ross Ethier, Ph.D., Department of Biomedical Engineering, Georgia Institute of Technology

Committee:

Andrés J. García, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

Rudolph L. Gleason, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

J. Brandon Dixon, Ph.D., School of Mechanical Engineering, Georgia Institute of Technology

Ian A. Sigal, Ph.D., Department of Bioengineering, University of Pittsburgh

Finite Element Modeling of Optic Nerve Head Biomechanics in a Rat Model of Glaucoma

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 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. The results from this work can serve to inform future modeling studies on the rat ONH 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.