Racial Variations in Optic Nerve Head Structure and Biomechanics

视神经头结构和生物力学的种族差异

• 批准号: 7735579
• 负责人: J CRAWFORD DOWNS
• 金额: $ 30.5万
• 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: 2008-12-01 至 2011-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7735579
• 关键词: Affect; African; Age; Architecture; Astrocytes; Axonal Transport; Basement membrane; Biomechanics; Blood flow; Cell Death; Cellular biology; Cessation of life; Clinical; Computer Simulation; Connective Tissue; Data; Development; Diagnostic; Disease Progression; Elements; European; Event; Eye; Functional disorder; Glaucoma; Goals; Human; Immersion Investigative Technique; Individual; Lead; Link; Measures; Mechanics; Methods; Modeling; Morphology; Optic Disk; Parents; Patients; Physiologic Intraocular Pressure; Physiological; Play; Predisposition; Property; Retinal Ganglion Cells; Risk; Risk Factors; Role; Sclera; Stress; Stretching; Structure; Testing; Tissue Donors; Tissues; Variant; age related; biomechanical engineering; capillary; digital; high risk; mechanical behavior; novel; public health relevance; racial difference; reconstruction; research study; 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 patients 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 racial differences in optic nerve head (ONH) biomechanics importantly contribute to this difference in risk. It is still unclear, however, how IOP triggers the cascade of events that lead to retinal ganglion cell death. 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 African ancestry and the mechanical effects of elevated IOP is still unclear. How do racial variations 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 patients of African descent? To answer these questions, we will use novel methods to elucidate the relationship between ancestry 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 racial variations 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. 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 patients of African descent have higher risk of development and progression of the disease. We propose to measure the racial variation 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 African ancestry 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。有令人信服的证据表明，在眼压水平升高的情况下，非洲人后裔患者青光眼损伤发生和进展的风险要大得多。在本提案中，我们检验了这样一个假设：视神经乳头 (ONH) 生物力学的种族差异对这种风险差异有重要影响。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。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，非洲血统与眼压升高的机械效应之间的关系仍不清楚。 ONH 结构和生物力学的种族差异如何增加其对 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僵硬在非洲人后裔患者青光眼进展风险增加中发挥什么作用？为了回答这些问题，我们将使用新方法来阐明祖先与 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。该项目的直接目标是描述 ONH 生物力学的种族差异，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，我们将对来自非洲和欧洲血统的捐赠者的人类 ONH 组织进行数字三维重建，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和升高的 IOP 水平的生物力学反应。公众健康相关性 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，非洲裔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的种族差异。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，以阐明非洲血统与青光眼易感性之间的联系。