Age-related changes 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。患者年龄是青光眼损害发生和发展的最重要的危险因素之一，无论青光眼的分期或发生青光眼时的眼压水平。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。我们假设，与年龄相关的ONH生物力学改变对增加人类老年性ONH的易感性有重要作用。 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，患者年龄与高眼压的机械效应之间的关系仍不清楚。与老年患者一样，ONH是如何改变的，从而增加了其对眼压的易感性？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青光眼进展的年龄相关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与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。这个项目的近期目标是描述ONH生物力学中与年龄相关的差异，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。为了实现眼前的目标，我们将建立年轻人和老年人ONH组织的数字三维重建，量化每次重建中ONH结缔组织的结构，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。我们还将把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的易感性和临床行为的增加联系起来。与公共卫生相关。长期以来，眼压升高一直被认为是青光眼对视神经头(ONH)损害的原因之一，年龄较大的患者发生和发展疾病的风险更高。我们建议测量与年龄相关的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来创建与年龄相关的眼压升高对ONH的机械效应的计算模型，以阐明年龄增长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). 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.