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

视神经头结构和生物力学的年龄和种族相关差异

• 批准号: 8635351
• 负责人: J CRAWFORD DOWNS
• 金额: $ 36.41万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 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 2016-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8635351
• 关键词: Affect; African; Age; Architecture; Area; Astrocytes; Automobile Driving; Axon; Biomechanics; Blindness; Blood capillaries; Blood flow; Cadaver; Cell Death; Clinical; Computer Simulation; Connective Tissue; Data; Development; Diagnostic; Disease Progression; Elderly; Elements; European; Event; Exhibits; Eye; Functional disorder; Future; Glaucoma; Goals; Grant; Homeostasis; Human; Imaging Device; Immersion Investigative Technique; Individual; Injury; Link; Measures; Mechanical Stress; Mechanics; Mediator of activation protein; Methods; Modeling; Morphology; Neuroglia; Nutrient; Optic Disk; Optic Nerve Injuries; Optical Coherence Tomography; Patients; Pattern; Physiologic Intraocular Pressure; Pia Mater; Play; Predisposition; Property; Race; Resolution; Retinal Ganglion Cells; Risk; Risk Factors; Role; Sclera; Stretching; Structure; Testing; Tissue Donors; Tissues; Translating; Variant; Weight-Bearing state; age related; biomechanical engineering; capillary; density; digital; high risk; insight; normal aging; novel; public health relevance; racial difference; 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). 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.

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。有令人信服的证据表明，非洲血统的老年人和个体在IOP水平升高时面临青光眼损害的发作和进展的风险要大得多。在此提案中，我们检验了以下假设：ONH生物力学上与年龄和种族有关的差异可能会导致这种风险差异。使用高分辨率，荧光，三维（3D）ONH的重建以及生物力学工程原理，我们将研究升高IOP在青光眼中的机械效应。但是，尚不清楚年龄，非洲血统和升高IOP的机械影响之间的关系尚不清楚。 ONH结构和生物力学上与年龄和种族有关的差异如何增加其对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？在非洲血统和非洲血统的个体中，椎板纤维菌和周围巩膜的结构僵硬在增加的绿木糖体进展风险方面有什么作用？为了回答这些问题，我们将使用新颖的方法来阐明年龄，种族和IOP诱导的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ONH生物力学与年龄和种族有关的差异，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，我们将从非洲和欧洲下降的捐助者中建立数字三维重建，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IOP正常和高架IOP水平的生物机械响应。