Age- and Race-related Differences in Optic Nerve Head Structure and Biomechanics

描述（由申请人提供）：长期以来一直认为眼内压（IOP）升高是视神经乳头（ONH）昏迷性损伤的原因。有令人信服的证据表明，老年人和非洲裔个体在IOP水平升高时发生青光眼损害和进展的风险更大。在这个提议中，我们检验了年龄和种族相关的ONH生物力学差异可能导致这种风险差异的假设。使用高分辨率，荧光，三维（3D）重建的ONH，和生物力学工程的原则，我们将研究青光眼眼压升高的机械效应。然而，年龄增长、非洲血统和IOP升高的机械效应之间的关系仍不清楚。年龄和种族相关的ONH结构和生物力学差异如何增加其对IOP的敏感性？ONH结缔组织的坚固性是了解个体青光眼易感性的关键吗？筛板和视乳头周围巩膜的结构刚度在老年人和非洲裔个体的青光眼进展风险增加中起什么作用？为了回答这些问题，我们将使用新的方法来阐明年龄，种族和IOP诱导的ONH结缔组织变形之间的关系。“ONH生物力学”是指在ONH和视乳头周围巩膜中IOP和结缔组织结构刚度（组织结构和材料性质的组合）之间的相互作用。该项目的直接目标是描述年龄和种族相关的ONH生物力学差异，并阐明其对ONH易感性的影响。我们的长期目标是开发临床诊断和干预措施，旨在管理青光眼发展和进展中的每个重要生物力学风险因素。为了实现我们的近期目标，我们将建立来自非洲和欧洲血统供体的人类ONH组织的数字三维重建，量化每个重建中的ONH结缔组织结构，并建立ONH结缔组织的计算有限元模型，以估计其对正常和升高的IOP水平的生物力学反应。

DESCRIPTION (provided by applicant): Elevated intraocular pressure (IOP) has long been assumed to play a causative role in glaucomatous damage to the optic nerve head (ONH). There is compelling evidence to suggest that the elderly and individuals of African descent are at much greater risk for the onset and progression of glaucomatous damage at elevated levels of IOP. In this proposal, we test the hypothesis that age- and race-related differences in ONH biomechanics may contribute to this difference in risk. Using high-resolution, fluorescent, three-dimensional (3D) reconstructions of the ONH, and principles of biomechanical engineering, we will study the mechanical effects of elevated IOP in glaucoma. However, the relationship between advancing age, African ancestry, and the mechanical effects of elevated IOP is still unclear. How do age- and race-related differences in ONH structure and biomechanics increase its susceptibility to IOP? Is the robustness of the ONH connective tissues the key to understanding individual susceptibility to glaucoma? What role does the structural stiffness of the lamina cribrosa and peripapillary sclera play in the increased risk for glaucomatous progression in the elderly and in individuals of African descent? To answer these questions, we will use novel methods to elucidate the relationship between age, race, and the IOP-induced deformation of ONH connective tissues. By "ONH biomechanics" we mean the interactions between IOP and connective tissue structural stiffness (the combination of tissue architecture and material properties) in the ONH and peripapillary sclera. The immediate goals of this project are to characterize age- and race-related differences in ONH biomechanics and elucidate their effects on ONH susceptibility. Our long-term goal is to develop clinical diagnostics and interventions designed to manage each important biomechanical risk factor in the development and progression of glaucoma. To accomplish our immediate goals, we will build digital three-dimensional reconstructions of human ONH tissues from donors of African and European descent, quantify the ONH connective tissue architecture within each reconstruction, and build computational finite element models of the ONH connective tissues to estimate their biomechanical response to normal and elevated levels of IOP.