The influence of ocular remodeling on glaucoma

摘要 青光眼是世界范围内导致失明的主要原因，但青光眼视网膜神经节细胞损伤的原因 对视神经头(ONH)的认识还不完全。眼压升高被认为是主要的 青光眼的病因，但流行病学研究发现，中度或高度近视是一个独立的危险因素。 目前，这两种疾病之间的联系尚不清楚。我们提出了一种生物力学方法 这种相互作用的基础。我们的中心假设是巩膜和ONH重塑导致高眼压 近视是增加后续病理性ONH重塑和青光眼风险的诸多因素之一 在以后的生活中。随着近视在世界部分地区达到流行比例，以及近视的流行 青光眼持续增加，了解这些疾病过程的基本机制是 危急时刻。 我们将利用我们独特的实验性近视和青光眼的树鼠模型，体内的组合 和体外实验，并在硅胶多尺度模拟工具中检查生物力学基础 近视和青光眼之间的联系。这笔赠款将集中在三个主要感兴趣的领域：1)我们将研究 高度近视发生过程中巩膜和ONH的眼生物力学变化 树懒。2)我们将确定导致高度近视的巩膜重塑是否会使动物倾向于 促进实验性青光眼病理性ONH重塑和轴突丢失。以及，3)我们将 用多尺度模型阐明青光眼和高眼压的相互作用的生物力学机制 近视。这一知识将被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.