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: 7998165
• 负责人: J CRAWFORD DOWNS
• 金额: $ 29.19万
• 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/7998165
• 关键词: Affect; African; Age; Architecture; Astrocytes; Axonal Transport; Basement membrane; Biomechanics; Blood capillaries; 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; Health; 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; 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，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，非洲血统的患者在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：视神经头（ONH）生物力学的种族差异重要地有助于这种风险差异。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。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，非洲血统与IOP升高的机械影响之间的关系尚不清楚。 ONH结构和生物力学的种族变化如何增加其对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？在非洲血统患者中，拉米娜乳纤维和围层巩膜的结构僵硬在增加的青光眼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祖先与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生物力学的种族变化，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。长期以来，人们一直认为公共卫生相关性升高（IOP）长期以来在胶状神经头（ONH）中发挥了致病作用，而非洲血统患者的发育和发展风险更高。我们建议测量ONH结构的种族变化和IOP诱导的生物力学反应。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年龄相关的机械效应的计算模型，以阐明非洲血统与绿木敏感性之间的联系。