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

• 批准号: 9765319
• 负责人: Massimo Antonio Fazio
• 金额: $ 36.88万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-01 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9765319
• 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

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：视神经头(ONH)生物力学被认为在视神经损伤的病理生理机制中起着关键作用。 原发性开角型青光眼。ONH生物力学是由眼内相互作用驱动的 压力(IOP)、脑脊液压力(CSFP)和结缔组织结构刚度(组合 组织结构和材料特性)在ONH和巩膜。计算和实验研究 在动物模型中，ONH微环境中的应变(组织拉伸)受到强烈影响 巩膜的结构刚性和筛板(LC)的形态和密度。实验 研究表明，随着青光眼的发展，这些结构也会随着年龄和种族的不同而变化。 非洲裔(AD)组与欧洲裔(ED)组，也可能与角膜变异有关 厚度和硬度。这一点很重要，因为年龄、青光眼严重程度、AD以及角膜厚度和硬度 与眼压无关的OAG最一致的危险因素。这项研究的目的是：1)发现 LC的形态和巩膜硬度如何决定ONH的力学行为 眼压和CSFP的变化以及2)确定巩膜、ONH和ONH的结构刚度的差异 角膜老化、青光眼和跨种族人群与ONH劳损有关。设计：这项研究将 利用一种新的资源，阿拉巴马州活眼项目。这项计划提供了获取脑死亡器官的途径 器官采购前的捐赠者。与近亲讨论并征得同意，进行眼科检查 将进行生物测定，然后对体内ONH菌株进行量化，以响应两者的变化 使用光谱域光学相干断层扫描(SDOCT)进行IOP和CSFP检查。在器官采购之后， 用激光电子散斑干涉术和ONH测量巩膜结构刚度 显微结构将在ONH的数字3D组织学表观重建中进行量化。多变量 模型将用于确定巩膜僵硬和ONH形态对ONH应变的影响，以及这些 老年眼和青光眼、AD或ED供者的眼睛和角膜的变异有不同的关系 僵硬。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 眼部影像和生物统计学数据，并将阐明与ONH变化相关的致病机制 在AD和ED组中，随年龄、青光眼而观察的生物力学，并与测量 角膜厚度和硬度。这些信息不仅将为机械相关技术的发展提供信息 青光眼易感性的生物标志物：了解巩膜僵硬和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方法的开发 ONH的应变驱动重塑。 好了！