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

描述(申请人提供)：长期以来，高眼压(IOP)一直被认为是青光眼对视神经头(ONH)损害的原因之一。有令人信服的证据表明，老年人和非洲裔人在眼压升高时发生和发展青光眼损害的风险要大得多。在这项建议中，我们测试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。我们将利用高分辨率、荧光、ONH的三维(3D)重建和生物力学工程原理，研究青光眼高眼压的力学效应。然而，年龄增长、非洲血统和高眼压的机械效应之间的关系仍然不清楚。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的易感性？ONH结缔组织的健壮性是了解个体青光眼易感性的关键吗？筛板和乳头状巩膜周围的结构僵硬在老年人和非洲裔人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。所谓“ONH生物力学”，我们指的是ONH和巩膜周围结缔组织结构硬度(组织结构和材料特性的组合)与眼压之间的相互作用。该项目的近期目标是描述ONH生物力学中与年龄和种族相关的差异，并阐明它们对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。为了实现我们的眼前目标，我们将建立来自非洲和欧洲血统捐赠者的ONH组织的数字三维重建，量化每次重建中的ONH结缔组织结构，并建立ONH结缔组织的计算有限元模型，以评估它们对正常和高眼压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.