Investigating the Relationship Between the Structure and Mechanical Behavior of the Lamina Cribrosa

研究筛板结构与力学行为之间的关系

基本信息

批准号：
1727104
负责人：
Thao Nguyen
金额：
$ 34.24万
依托单位：
Johns Hopkins University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2021-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1727104&HistoricalAwards=false
关键词：
Investigating Relationship Between Structure Mechanical

项目摘要

Glaucoma is a blinding disease caused by the progressive death of retinal ganglion cells and their axons in the lamina cribrosa. The lamina cribrosa is a fenestrated connective tissue structure in the optic nerve head that mechanically supports axons as they exit the eye. Glaucoma is the leading cause of blindness in the US, affecting an estimated 3 million Americans. The incidence and severity of the disease strongly correlate with the intraocular pressure, though the level of the intraocular pressure at which glaucoma damage is detected varies widely. Lowering the intraocular pressure can slow axon loss. The effectiveness of the treatment varies among patients and 10% of patients diagnosed with glaucoma eventually go blind. The PIs hypothesize that deformation caused by the intraocular pressure in the optic nerve head causes axonal damage. Moreover regional variations in the microstructure of the lamina cribrosa lead to regions of greater damage. In this project, the PIs will measure the pressure-induced strains and the structure of the lamina cribrosa. These will be used to create models of the lamina cribrosa to determine why certain regions exhibit more deformation and higher stress levels. Understanding the relationship between the optic nerve head structure and deformation may lead to the identification of new structural biomarkers for the early detection of glaucoma using non-invasive imaging and to the development of more effective patient-specific treatment strategies. Axon damage produces permanent vision loss in adult glaucoma and early detection is key to preserving vision. The project will also benefit engineering education by providing research opportunities to graduate, undergraduate and high school students that involves state of the art experimental and modeling methods. The objective of the research is to investigate the extent that anatomical structure and microstructural features lead to regional variations in the strain and stress levels. We will apply a recently developed inflation test, which uses multiphoton imaging and digital volume correlation, to measure the three-dimensional deformation field in the lamina cribrosa and surrounding peripapillary sclera. The inflation test method also yields measurements of the anatomical structure of the optic nerve head tissues. We will analyze these for regional differences and for eye-specific correlations between the structural and strain measurements. The data will be used to develop specimen-specific micromechanical models to study the deformation kinematics of the fibrous network microstructure of the lamina cribrosa and the structure-properties relationship of the optic nerve head tissue. Finally, the outcomes of the experiments and lower scale micromechanical models will be used to develop specimen- specific finite element models of the optic nerve head and sclera to systematically evaluate the contributions of microstructural and anatomic features to the spatial variations in the strain and stress state. The work will advance fundamental understanding of the biomechanics of the optic nerve head and elucidate the relationship between the structure and material behavior through computational modeling and statistical analysis of the eye-specific LC anatomical structure, microstructure, deformation.

青光眼是一种致盲性疾病，由筛板中视网膜神经节细胞及其轴突的进行性死亡引起。筛板是视神经乳头中的有窗结缔组织结构，在轴突离开眼睛时机械支撑轴突。青光眼是美国导致失明的主要原因，估计影响了 300 万美国人。该疾病的发病率和严重程度与眼压密切相关，尽管检测到青光眼损伤的眼压水平差异很大。降低眼压可以减缓轴突损失。治疗效果因患者而异，10% 被诊断患有青光眼的患者最终会失明。 PI 假设视神经头眼内压引起的变形会导致轴突损伤。此外，筛板微观结构的区域差异会导致损伤更大的区域。在这个项目中，PI 将测量压力引起的应变和筛板的结构。这些将用于创建筛板模型，以确定为什么某些区域表现出更大的变形和更高的应力水平。了解视神经乳头结构和变形之间的关系可能有助于识别新的结构生物标志物，用于使用非侵入性成像早期检测青光眼，并开发更有效的针对患者的治疗策略。轴突损伤会导致成人青光眼永久性视力丧失，早期发现是保持视力的关键。该项目还将为研究生、本科生和高中生提供涉及最先进的实验和建模方法的研究机会，从而使工程教育受益。该研究的目的是调查解剖结构和微观结构特征导致应变和应力水平的区域变化的程度。我们将应用最近开发的膨胀测试，该测试使用多光子成像和数字体积相关性来测量筛板和周围视乳头周围巩膜的三维变形场。膨胀测试方法还可以测量视神经乳头组织的解剖结构。我们将分析这些结构和应变测量之间的区域差异以及眼睛特定的相关性。这些数据将用于开发样本特定的微机械模型，以研究筛板纤维网络微结构的变形运动学和视神经乳头组织的结构-特性关系。最后，实验结果和较小规模的微机械模型将用于开发视神经乳头和巩膜的标本特定有限元模型，以系统地评估微观结构和解剖特征对应变和应力状态空间变化的贡献。这项工作将通过对眼睛特定的 LC 解剖结构、微观结构、变形进行计算建模和统计分析，增进对视神经乳头生物力学的基本理解，并阐明结构与材料行为之间的关系。

项目成果

期刊论文数量（7）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

The Effects of Glaucoma on the Pressure-Induced Strain Response of the Human Lamina Cribrosa

青光眼对人筛板压力诱发应变反应的影响

DOI：
10.1167/iovs.61.4.41
发表时间：
2020-04
期刊：
Investigative Opthalmology & Visual Science
影响因子：
0
作者：
Midgett, Dan;Liu, Baiyun;Ling, Yik Tung;Jefferys, Joan L.;Quigley, Harry A.;Nguyen, Thao D.
通讯作者：
Nguyen, Thao D.

The inflation response of the human lamina cribrosa and sclera: Analysis of deformation and interaction

人体筛板和巩膜的膨胀反应：变形和相互作用分析