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: 7447498
• 负责人: J CRAWFORD DOWNS
• 金额: $ 38.83万
• 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: 2008-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7447498
• 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; Human; Immersion Investigative Technique; Individual; Lead; Link; Measures; Mechanics; Methods; Modeling; Morphology; Nutrient; Optic Disk; Parents; Patients; Physiologic Intraocular Pressure; Physiological; Play; Predisposition; Property; Public Health; Range; Retinal Ganglion Cells; Risk; Risk Factors; Role; Sclera; Staging; Stress; Structure; Testing; Thinking; Tissues; Variant; age related; aged; biomechanical engineering; digital; human old age (65+); 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，人们一直认为眼内压（IOP）在胶状神经头（ONH）中起着致病作用。患者年龄是青光眼损害发作和进展的最重要的风险因素之一，无论是青光眼的阶段或发生的眼内压力（IOP）的水平。但是，目前尚不清楚IOP如何触发导致视网膜神经节细胞死亡的一系列级联事件。我们假设ONH生物力学与年龄相关的改变对人类年龄较大的ONH的易感性提高了。 使用ONH的三维（3D）重建以及生物力学工程原理，我们研究了升高IOP在青光眼中的机械效应。但是，患者年龄与IOP升高的机械影响之间的关系尚不清楚。在老年患者中，ONH如何改变，以提高其对IOP的敏感性？ ONH结缔组织的鲁棒性是了解个人对青光眼易感性的关键吗？在与年龄相关的青光眼进展风险增加的情况下，椎板纤维菌和围层巩膜的结构刚度在何种作用？为了回答这些问题，我们将使用新颖的方法来阐明年龄与IOP引起的ONH结缔组织变形之间的关系。 通过“ ONH生物力学”，我们的意思是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。该项目的直接目标是表征与年龄相关的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旨在管理青光眼发展和发展中每个重要的生物力学风险因素的临床诊断和干预措施。为了实现我们的直接目标，我们将建立对年轻人和老年人组织组织的数字三维重建，量化每个重建内的ONH结缔组织结构，并构建ONH结缔组织的计算有限元模型，以估算其对正常和升高IOP水平的生物力学响应。我们还将将与年龄相关的ONH结构，组织僵硬和生物力学行为的变化与老化ONH的易感性和临床行为相关联。公共卫生相关性。长期以来，人们一直认为眼内压（IOP）升高在视神经头（ONH）的青光眼损害中起致病作用，并且老年患者的发育和发展风险更高。我们建议衡量与年龄相关的ONH结构和IOP诱导的生物力学反应的差异。然后，使用生物力学工程的原理，我们将使用这些数据来创建升高IOP对ONH的年龄相关机械效应的计算模型，以阐明年龄与青光眼易感性之间的联系。