Mechanics of Intraocular Pressure Increase Associated with Genetic Factors

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The research objective of this award is to use information emerging from glaucoma genetics to inform understanding of the biomechanical processes by which eye pressure is maintained. An interdisciplinary approach combines engineering analyses and molecular genetic tools to study how molecular genetic processes can affect the mechanics problem that leads to elevated eye pressure. The research includes molecular analysis of circulatory fluids from cultured media and donor eyes. Of particular relevance is quantification of myocilin, a protein made by ocular tissues that has been implicated in traits that involve elevated eye pressure. This information will be incorporated in mathematical/computer models to study a key aspect of the eye?s circulation system- the interaction of ocular fluid and fine meshwork tissues through which the fluid percolates. The fluid-solid interaction results in forces and pressures that can: (1) alter the tissue?s shape and flow and thereby produce increased pressure and (2) provide stimulus to initiate a biological signaling process to alter the flow, and thereby control pressure.Research on the mechanobiology of ocular tissue and elevated eye pressure has direct application to both ocular hypertension and glaucoma. Ocular hypertension affects about 10% of the population over age 40. Millions of people worldwide eventually develop glaucoma, making it one of the leading causes of irreversible blindness, at great personal and societal costs. The knowledge gained will also be relevant to organs such as the kidney, the liver and the lymphatic system, having mesh-like tissues similar to the trabecular meshwork of the eye. The education plan includes training of 3 graduate and 6 Research Experience for Undergraduate students. These will come from the two UM campuses and from neighboring institutions to expand the project?s impact. Since the project combines cutting-edge research from diverse technical fields, it offers the students an opportunity to work in a unique, interdisciplinary setting.