Racial Variations in Optic Nerve Head Structure and Biomechanics

描述(申请人提供)：长期以来，高眼压(IOP)一直被认为是青光眼对视神经头(ONH)损害的原因之一。有令人信服的证据表明，在眼压升高的情况下，非洲裔患者发生和发展青光眼损害的风险要大得多。在这项建议中，我们测试了这样一个假设，即视神经头(ONH)生物力学的种族差异对这种风险差异有重要影响。然而，眼压如何触发导致视网膜神经节细胞死亡的一连串事件仍不清楚。利用ONH的三维重建和生物力学工程原理，我们研究了青光眼高眼压的力学效应。然而，非洲血统与高眼压的机械效应之间的关系仍然不清楚。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结缔组织的健壮性是了解个体青光眼易感性的关键吗？筛板和乳头周围巩膜的结构僵硬在非洲裔患者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祖先和IOP诱导的ONH结缔组织变形之间的关系。所谓“ONH生物力学”，我们指的是ONH和巩膜周围结缔组织结构硬度(组织结构和材料特性的组合)与眼压之间的相互作用。该项目的直接目标是描述ONH生物力学中的种族差异，并阐明它们对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，旨在管理青光眼发展和进展中的每个重要生物力学风险因素。为了实现我们的眼前目标，我们将建立来自非洲和欧洲血统捐赠者的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，以评估它们对正常和高眼压水平的生物力学反应。公共卫生相关性高眼压(IOP)长期以来一直被认为是青光眼对视神经头(ONH)损害的原因，非洲裔患者发生和发展疾病的风险更高。我们建议测量ONH结构和IOP诱导的生物力学反应的种族差异。然后，利用生物力学工程的原理，我们将使用这些数据来创建与年龄相关的眼压升高对ONH的机械影响的计算模型，以阐明非洲血统和青光眼易感性之间的联系。

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.