Age-related changes in optic nerve head structure and biomechanics

描述（由申请人提供）：长期以来一直认为眼内压（IOP）升高是视神经乳头（ONH）昏迷性损伤的原因。患者年龄是青光眼损害发生和进展的最重要的风险因素之一，无论青光眼的分期或发生时的眼内压（IOP）水平如何。然而，目前尚不清楚IOP如何触发导致视网膜神经节细胞死亡的级联事件。我们假设年龄相关的ONH生物力学的改变对人类老年ONH易感性的增加有重要贡献。 使用三维（3D）重建的ONH，和生物力学工程的原则，我们已经研究了青光眼眼压升高的机械效应。然而，患者年龄与IOP升高的机械效应之间的关系仍不清楚。老年患者的ONH是如何改变的，从而增加其对IOP的敏感性？ONH结缔组织的坚固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刚度在与年龄相关的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年龄和眼压诱导的ONH结缔组织变形之间的关系。 “ONH生物力学”是指在ONH和视乳头周围巩膜中IOP和结缔组织结构刚度（组织结构和材料性质的组合）之间的相互作用。该项目的直接目标是描述年龄相关的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。为了实现我们的近期目标，我们将建立年轻和老年人ONH组织的数字三维重建，量化每个重建中的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。我们还将ONH结构、组织硬度和生物力学行为的年龄相关变化与老年ONH的易感性增加和临床行为相关。公共卫生相关性。长期以来，人们一直认为眼内压（IOP）升高是导致视神经乳头（ONH）昏迷性损伤的原因，老年患者发生和进展疾病的风险更高。我们建议测量年龄相关的ONH结构和IOP诱导的生物力学反应的差异。然后，利用生物力学工程的原理，我们将使用这些数据创建IOP升高对ONH的年龄相关机械影响的计算模型，以阐明年龄增长与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). 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.