Age-related changes in optic nerve head structure and biomechanics

视神经乳头结构和生物力学与年龄相关的变化

• 批准号: 8078086
• 负责人: J CRAWFORD DOWNS
• 金额: $ 35.98万
• 依托单位: LEGACY EMANUEL HOSPITAL AND HEALTH CENTER
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-06-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8078086
• 关键词: Age; Age-Years; Architecture; Behavior; Biomechanics; Blood flow; Cell Death; Clinical; Computer Simulation; Connective Tissue; Data; Development; Diagnostic; Diffusion; Disease Progression; Elderly; Elements; European; Event; Eye; Glaucoma; Goals; Health; Human; Immersion Investigative Technique; Individual; Lead; Link; Measures; Mechanics; Methods; Modeling; Morphology; Nutrient; Optic Disk; Parents; Patients; Physiologic Intraocular Pressure; Physiological; Play; Predisposition; Property; Retinal Ganglion Cells; Risk; Risk Factors; Role; Sclera; Staging; Stress; Structure; Testing; Tissues; Variant; age related; aged; biomechanical engineering; digital; high risk; human old age (65+); mechanical behavior; novel; older patient; reconstruction; response; therapy design

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). Patient age is among the most important risk factors for the onset and progression of glaucomatous damage, regardless of the stage of glaucoma or the level of intraocular pressure (IOP) at which it has occurred. It is still unclear, however, how IOP triggers the cascade of events that lead to retinal ganglion cell death. We hypothesize that age-related alterations in ONH biomechanics contribute importantly to the increased susceptibility of the aged ONH in humans. Using three-dimensional (3D) reconstructions of the ONH, and principles of biomechanical engineering, we have studied the mechanical effects of elevated IOP in glaucoma. However, the relationship between patient age and the mechanical effects of elevated IOP is still unclear. How is the ONH altered as in the older patient that increases 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 age-related risk for glaucomatous progression? To answer these questions, we will use novel methods to elucidate the relationship between age and the IOP- induced deformation of ONH connective tissues are needed. 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-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 young and old human ONH tissues, 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. We will also correlate the age-related variations in ONH architecture, tissue stiffness, and biomechanical behavior with the increased susceptibility and clinical behavior of the aged ONH. PUBLIC HEALTH RELEVANCE. Elevated intraocular pressure (IOP) has long been assumed to play a causative role in glaucomatous damage to the optic nerve head (ONH), and older patients have higher risk of development and progression of the disease. We propose to measure the age-related differences in ONH structure and IOP-induced biomechanical response. Then, using the principles of biomechanical engineering, we will use these data to create computational models of the age-related mechanical effects of elevated IOP on the ONH to elucidate the link between advancing age and glaucomatous susceptibility.

描述（由申请人提供）：长期以来，眼内压（IOP）升高一直被认为是青光眼性视神经乳头（ONH）损伤的致病因素。无论青光眼处于哪个阶段或发生时的眼压 (IOP) 水平如何，患者年龄都是青光眼损伤发生和进展的最重要的危险因素之一。然而，目前尚不清楚眼内压如何引发一系列事件，导致视网膜神经节细胞死亡。我们假设 ONH 生物力学中与年龄相关的变化对人类老年 ONH 的易感性增加有重要影响。 利用 ONH 的三维 (3D) 重建和生物力学工程原理，我们研究了青光眼眼压升高的机械效应。然而，患者年龄与眼压升高的机械效应之间的关系仍不清楚。老年患者的 ONH 是如何改变的，从而增加了 IOP 的易感性？ ONH 结缔组织的稳健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与年龄相关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和 IOP 引起的 ONH 结缔组织变形之间的关系。 “ONH 生物力学”是指 ONH 和视乳头周围巩膜中 IOP 与结缔组织结构刚度（组织结构和材料特性的组合）之间的相互作用。该项目的近期目标是描述 ONH 生物力学中与年龄相关的差异，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，旨在管理青光眼发生和进展过程中的每个重要的生物力学危险因素。为了实现我们的近期目标，我们将建立年轻和老年人类 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估计其对正常情况的生物力学反应和眼压水平升高。我们还将把 ONH 结构、组织硬度和生物力学行为中与年龄相关的变化与老年 ONH 增加的易感性和临床行为联系起来。公共卫生相关性。长期以来，眼内压（IOP）升高一直被认为是青光眼性视神经乳头（ONH）损伤的致病因素，而老年患者发生和进展该疾病的风险较高。我们建议测量 ONH 结构和 IOP 引起的生物力学反应与年龄相关的差异。然后，利用生物力学工程原理，我们将利用这些数据创建眼压升高对 ONH 的与年龄相关的机械效应的计算模型，以阐明年龄增长与青光眼易感性之间的联系。