Investigating the Relationship Between the Structure and Mechanical Behavior of the Lamina Cribrosa

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Glaucoma is a blinding disease caused by the progressive death of retinal ganglion cells and their axons in the lamina cribrosa. The lamina cribrosa is a fenestrated connective tissue structure in the optic nerve head that mechanically supports axons as they exit the eye. Glaucoma is the leading cause of blindness in the US, affecting an estimated 3 million Americans. The incidence and severity of the disease strongly correlate with the intraocular pressure, though the level of the intraocular pressure at which glaucoma damage is detected varies widely. Lowering the intraocular pressure can slow axon loss. The effectiveness of the treatment varies among patients and 10% of patients diagnosed with glaucoma eventually go blind. The PIs hypothesize that deformation caused by the intraocular pressure in the optic nerve head causes axonal damage. Moreover regional variations in the microstructure of the lamina cribrosa lead to regions of greater damage. In this project, the PIs will measure the pressure-induced strains and the structure of the lamina cribrosa. These will be used to create models of the lamina cribrosa to determine why certain regions exhibit more deformation and higher stress levels. Understanding the relationship between the optic nerve head structure and deformation may lead to the identification of new structural biomarkers for the early detection of glaucoma using non-invasive imaging and to the development of more effective patient-specific treatment strategies. Axon damage produces permanent vision loss in adult glaucoma and early detection is key to preserving vision. The project will also benefit engineering education by providing research opportunities to graduate, undergraduate and high school students that involves state of the art experimental and modeling methods. The objective of the research is to investigate the extent that anatomical structure and microstructural features lead to regional variations in the strain and stress levels. We will apply a recently developed inflation test, which uses multiphoton imaging and digital volume correlation, to measure the three-dimensional deformation field in the lamina cribrosa and surrounding peripapillary sclera. The inflation test method also yields measurements of the anatomical structure of the optic nerve head tissues. We will analyze these for regional differences and for eye-specific correlations between the structural and strain measurements. The data will be used to develop specimen-specific micromechanical models to study the deformation kinematics of the fibrous network microstructure of the lamina cribrosa and the structure-properties relationship of the optic nerve head tissue. Finally, the outcomes of the experiments and lower scale micromechanical models will be used to develop specimen- specific finite element models of the optic nerve head and sclera to systematically evaluate the contributions of microstructural and anatomic features to the spatial variations in the strain and stress state. The work will advance fundamental understanding of the biomechanics of the optic nerve head and elucidate the relationship between the structure and material behavior through computational modeling and statistical analysis of the eye-specific LC anatomical structure, microstructure, deformation.