The influence of ocular remodeling on glaucoma

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Abstract Glaucoma is a leading cause of blindness worldwide, yet the reason for retinal ganglion cell damage within the optic nerve head (ONH) is not fully understood. Elevated intraocular pressure (IOP) is considered the primary cause of glaucoma, but epidemiologic studies identify moderate or high myopia as an independent risk factor. Currently, the connection between these two diseases is unknown. We propose that there is a biomechanical basis underlying this interaction. Our central hypothesis is that scleral and ONH remodeling that leads to high myopia is one of many factors increasing the risk for subsequent pathologic ONH remodeling and glaucoma later in life. With myopia reaching epidemic proportions in portions of the world, and the prevalence of glaucoma continuing to increase, understanding the basic mechanisms underlying these disease processes is critical. We will leverage our unique tree shrew model of experimental myopia and glaucoma, a combination of in vivo and ex vivo experiments, and in silico multiscale simulation tools to examine the biomechanical basis for the link between myopia and glaucoma. The grant will focus on three primary areas of interest: 1) We will examine the ocular biomechanical changes that occur within the sclera and ONH during high myopia development in tree shrews. 2) We will determine whether scleral remodeling that leads to high myopia predisposes an animal to accelerated pathologic ONH remodeling and increased axon loss in experimental glaucoma. And, 3) We will use multiscale modeling to elucidate the interacting biomechanical mechanisms underlying glaucoma and high myopia. This knowledge will be used to develop novel targets for future glaucoma therapies.