Determinants of the Biomechanical Behavior of the Human Lamina Cribrosa

项目摘要 背景：视神经乳头（ONH）的生物力学被认为在视神经病变的病理生理学中起着关键作用。 原发性开角型青光眼（POAG）。ONH生物力学是由眼内 压力（IOP）、脑脊液压力（CSFP）和结缔组织结构刚度（组合 组织结构和材料性质）。计算和实验研究 在动物模型中，已经表明ONH微环境中的应变（组织拉伸）受到强烈影响， 通过巩膜的结构刚度和筛板（LC）的形态和密度。实验 研究表明，这些结构也随着青光眼的发展、年龄和种族而变化。 非洲裔（AD）与欧洲裔（艾德）的差异，也可能与角膜内皮细胞的变化有关。 厚度和硬度。这一点很重要，因为年龄、青光眼严重程度、AD和角膜厚度和硬度是影响青光眼发病率的重要因素。 与IOP无关的OAG最一致的风险因素。本研究的目的是：1）发现 LC的形态学和巩膜硬度如何决定ONH响应于 IOP和CSFP的变化，以及2）确定巩膜、ONH和 在老年人、青光眼患者和跨种族人群中观察到的角膜与ONH菌株有关。设计：本研究将 使用一种新的资源，亚拉巴马活眼计划。这个项目提供了获取脑死亡器官的途径 在器官采购之前。在与近亲讨论并同意后，进行眼部检查， 将进行生物测定，然后定量体内ONH菌株，以响应两者的变化。 使用谱域光学相干断层扫描（SDOCT）的IOP和CSFP。在器官采购之后， 巩膜结构刚度将用激光电子散斑干涉法和ONH测量。 将在ONH的数字3D组织学episcopic重建中量化微结构。多变量 模型将用于确定巩膜硬度和ONH形态对ONH应变的影响， 在老年和昏迷眼、AD或艾德供体眼以及角膜上皮细胞的变化中， 刚度影响：本研究提供了将巩膜和ONH生物力学与临床 眼部成像和生物统计学数据，并将阐明与ONH变化相关的致病机制 AD和艾德组中随年龄、青光眼观察到的生物力学， 角膜厚度和硬度。这些信息不仅将告知机械相关的发展， 青光眼易感性的生物标志物，了解巩膜硬度和ONH形态如何调节ONH 生物力学将指导新的非降眼压青光眼治疗的发展， 压力驱动的ONH重塑。 !

Project Abstract Background: Optic nerve head (ONH) biomechanics is thought to play a critical role in the pathophysiology of primary open angle glaucoma (POAG). ONH biomechanics is driven be the interactions between intraocular pressure (IOP), cerebrospinal fluid pressure (CSFP) and connective tissue structural stiffness (the combination of tissue architecture and material properties) in the ONH and sclera. Computational and experimental studies in animal models have suggested that strain (tissue stretch) in the ONH microenvironment is strongly influenced by the structural stiffness of the sclera and the morphology and density of the lamina cribrosa (LC). Experimental studies have shown that these structures also vary with the development of glaucoma, with age and across racial groups of African descent (AD) vs. European descent (ED) and may also be associated with variation in corneal thickness and rigidity. This is important since age, glaucoma severity, AD and corneal thickness and rigidity are the most consistent risk factors for OAG independent of IOP. The Objectives of this study are: 1) to discover how the morphology of the LC and scleral rigidity determine the mechanical behavior of the ONH in response to changes in IOP and CSFP and 2) to determine how differences in structural stiffness of the scleral, ONH and cornea seen in aging, with glaucoma and across racial groups are related to ONH strain. Design: This study will employ a novel resource, the Alabama Living Eye Project. This program affords access to brain-dead organ donors prior to organ procurement. Follow discussion and consent with the next-of-kin, an ocular exam with biometry will be performed, followed by the quantification of in-vivo ONH strain in response to changes in both IOP and CSFP using spectral domain optical coherence tomography (SDOCT). Following organ procurement, scleral structural stiffness will be measured with laser electronic speckle pattern interferometry and ONH microstructure will be quantified in digital 3D histologic episcopic reconstructions of the ONH. Multivariable models will be used to determine the impact of scleral rigidity and ONH morphology on ONH strain and if these relationships differ in aged and glaucomatous eyes, in eyes from AD or ED donors and with variations in corneal stiffness. Impact: This study provides the unique opportunity to link scleral and ONH biomechanics to clinical ocular imaging and biometrics data, and will elucidate the causative mechanisms related to the variation in ONH biomechanics seen with age, with glaucoma, across AD and ED groups and associated with measurement of corneal thickness and rigidity. Not only will this information inform the development of mechanistically relevant biomarkers for glaucoma susceptibility, understanding how scleral stiffness and ONH morphology modulate ONH biomechanics will guide the development of new non-IOP lowering glaucoma therapies targeted at altering strain-driven remodeling of the ONH. !