The influence of ocular remodeling on glaucoma

摘要 青光眼是世界范围内致盲的主要原因，但青光眼患者中视网膜神经节细胞损伤的原因是： 视神经乳头（optic nerve head，ONH）尚未完全了解。眼内压（IOP）升高被认为是主要的 近视是青光眼的主要病因，但流行病学研究将中度或高度近视确定为独立的风险因素。 目前，这两种疾病之间的联系尚不清楚。我们认为，有一个生物力学 这种互动的基础。我们的中心假设是巩膜和ONH重塑，导致高 近视是增加随后病理性ONH重塑和青光眼风险的众多因素之一 在以后的生活中随着近视在世界部分地区达到流行病的比例， 青光眼持续增加，了解这些疾病过程的基本机制是 很危险 我们将利用我们独特的实验性近视和青光眼树鼩模型，结合体内 和离体实验，并在硅片多尺度模拟工具，以检查的生物力学基础， 近视和青光眼之间的联系。赠款将集中在三个主要领域的兴趣：1）我们将研究 在高度近视发展过程中，巩膜和ONH内发生的眼生物力学变化， 树鼩2)我们将确定导致高度近视的巩膜重塑是否会使动物 加速病理性ONH重塑和增加实验性青光眼中的轴突损失。（3）我们将 使用多尺度建模来阐明青光眼和高眼压的相互作用的生物力学机制。 近视这些知识将用于开发未来青光眼治疗的新靶点。

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.