Determinants of the Biomechanical Behavior of the Human Lamina Cribrosa

人类筛板生物力学行为的决定因素

基本信息

批准号：
10238922
负责人：
Massimo Antonio Fazio
金额：
$ 35.78万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10238922
关键词：
3-Dimensional Acute Affect African Age Aging Alabama Animal Model Animals Architecture Behavior Biological Markers Biomechanics Biometry Blindness Brain Death Cell Death Cerebrospinal Fluid Pressure Characteristics Clinical Connective Tissue Consent Cornea Custom Data Development Disease European Eye Functional disorder Geometry Glaucoma Goals Histologic Histology Human Image Individual Injury Interferometry Intracranial Pressure Isometric Exercise Knowledge Lasers Link Longitudinal Studies Measurement Measures Mechanical Stress Mechanics Methods Modeling Morphology Neural Canal Optic Disk Optical Coherence Tomography Organ Donor Organ Procurements Pathologic Pathway interactions Patients Pattern Physiologic Intraocular Pressure Pia Mater Play Predisposition Primary Open Angle Glaucoma Property Race Resolution Resources Retinal Ganglion Cells Risk Risk Factors Role Science Sclera Severities Specialist Stretching Structure Testing Thick Tissues Validation Variant Weight-Bearing state aged axon injury base clinical care clinical practice computer studies density design digital disorder risk experimental study in vivo in vivo evaluation innovation mechanical behavior neurovascular next generation novel ocular imaging programs reconstruction relating to nervous system resilience response targeted treatment translaminar pressure gradient treatment strategy

项目摘要

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. !

项目摘要背景：视神经乳头（ONH）生物力学被认为在视神经乳头的病理生理学中发挥着关键作用。原发性开角型青光眼（POAG）。 ONH 生物力学是由眼内之间的相互作用驱动的压力（IOP）、脑脊液压力（CSFP）和结缔组织结构刚度（组合 ONH 和巩膜中的组织结构和材料特性）。计算和实验研究动物模型表明 ONH 微环境中的应变（组织拉伸）受到强烈影响巩膜的结构刚度以及筛板 (LC) 的形态和密度。实验性的研究表明，这些结构也随着青光眼的发展、年龄和种族的不同而变化。非洲后裔 (AD) 与欧洲后裔 (ED) 的群体，也可能与角膜的变异有关厚度和刚性。这一点很重要，因为年龄、青光眼严重程度、AD 以及角膜厚度和硬度都与独立于 IOP 的最一致的 OAG 风险因素。本研究的目标是：1）发现 LC 的形态和巩膜硬度如何决定 ONH 响应的机械行为 IOP 和 CSFP 的变化，以及 2) 确定巩膜、ONH 和老化、青光眼和跨种族群体的角膜与 ONH 应变有关。设计：本研究将使用一种新颖的资源，即阿拉巴马州活眼项目。该计划提供了获取脑死亡器官的机会器官获取前的捐赠者。与近亲讨论并同意后，进行眼科检查将进行生物测定，然后根据两者的变化对体内 ONH 应变进行量化使用谱域光学相干断层扫描 (SDOCT) 的 IOP 和 CSFP。器官获取后，巩膜结构刚度将通过激光电子散斑图案干涉仪和 ONH 进行测量微观结构将在 ONH 的数字 3D 组织学外显重建中进行量化。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，如果这些老年眼和青光眼眼、AD 或 ED 捐赠者的眼以及角膜的变化之间的关系有所不同刚性。影响：这项研究提供了将巩膜和 ONH 生物力学与临床联系起来的独特机会眼部成像和生物识别数据，并将阐明与 ONH 变化相关的致病机制生物力学随着年龄、青光眼、AD 和 ED 组的变化而变化，并与测量相关角膜厚度和硬度。这些信息不仅会为机械相关的开发提供信息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 生物力学将指导开发新的非眼压降低青光眼疗法，旨在改变 ONH 的应变驱动重塑。！