Biomechanical Interplay between Optic Nerve Head and Peripapillary Sclera

视神经乳头和视乳头周围巩膜之间的生物力学相互作用

基本信息

批准号：
10367335
负责人：
JUN LIU
金额：
$ 38.15万
依托单位：
OHIO STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-09-30 至 2026-08-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10367335
关键词：
3-Dimensional 3D ultrasound Address Affect African American Aftercare Age American Animal Model Axon Biochemical Biomechanics Blindness Complex Data Development Extracellular Matrix Eye Family suidae Foundations Glaucoma Human Image Imaging Techniques Individual Influentials Knowledge Lead Length Measurement Measures Mechanical Stress Mechanics Modification Modulus Myopia Optic Disk Optic Nerve Optics Patients Penetration Persons Physiologic Intraocular Pressure Placebos Play Predisposition Property Public Health Race Radial Randomized Recording of previous events Resolution Risk Risk Factors Role Sample Size Sclera Stress Techniques Testing Thick Tissues Vision axon injury base collagenase combat computer studies diagnostic strategy elastography feasibility testing genipin imaging modality in vivo innovation modifiable risk nerve damage novel novel diagnostics novel therapeutic intervention optic nerve disorder optical imaging porcine model power analysis radio frequency relating to nervous system response retinal imaging submicron success tomography treatment effect treatment group treatment response treatment strategy ultrasound

项目摘要

PROJECT SUMMARY/ABSTRACT Glaucoma affects about three million Americans and is a leading cause of blindness worldwide. Patients suffer from progressive optic neuropathy, for which intraocular pressure (IOP) induced mechanical insults at the optic nerve head (ONH) play a central role. Current treatments all aim to lower IOP. While these treatments are beneficial, many patients continue to lose vision with persistent optic nerve damage. There is a great need to identify other modifiable risk factors, based on which novel treatments may be developed to combat this public health problem. Biomechanically, the level of IOP-induced mechanical insults (i.e., stresses and strains) at the ONH are not determined by IOP alone. Computational studies have shown that peripapillary sclera (PPS) modulus and thickness are among the most influential factors. Interestingly, PPS biomechanical changes are implicated in older age, African American race, and high myopia, which have increased glaucoma risk. However, there is a knowledge gap in understanding the biomechanical interplay between ONH and PPS. For example, what PPS biomechanical properties are optimal and how PPS can be modified to mitigate IOP-induced mechanical insults at ONH remain poorly understood. We propose to use a high-resolution ultrasound elastography technique to resolve the complex mechanical responses of the ONH and PPS through full tissue thickness, and to begin to fill the knowledge gap. Using this technique, we will quantify ONH and PPS deformation in normal human donor eyes, those with PPS remodeling, and those with experimental modification of PPS properties. We will also further develop this technique for in vivo biomechanical imaging of the ONH and PPS in an animal model. Specifically, we propose the following aims: 1) test the prediction that ONH deformation is correlated with PPS deformation and different in older age and African American race, 2) test the prediction that ONH deformation is different in eyes with PPS remodeling, 3) test the prediction that ONH deformation is altered after biochemical stiffening or softening of the PPS, and 4) test the feasibility of in vivo ONH and PPS ultrasound elastography in a pig model. Successful completion of the proposed studies will establish a clear understanding of the biomechanical interplay between ONH and PPS, a key contributor to an individual eye’s mechanical susceptibility to IOP. Combined with the development of an in vivo biomechanical imaging technique, this knowledge will lay a foundation for novel diagnostic and treatment strategies to reduce glaucoma vision loss.

项目概要/摘要青光眼影响约三百万美国人，是全世界患者失明的主要原因。患有进行性视神经病变，眼内压（IOP）引起视神经机械损伤目前的治疗方法均旨在降低眼压。有益的是，许多患者因持续性视神经损伤而继续丧失视力，因此非常需要进行治疗。确定其他可改变的风险因素，在此基础上可以开发新的治疗方法来对抗这种公众从生物力学角度来看，眼压引起的机械损伤（即压力和应变）的水平。 ONH 不能仅由 IOP 确定计算研究表明视乳头周围巩膜 (PPS)。模量和厚度是影响最大的隐含因素，PPS 生物力学变化也是其中之一。与年龄较大、非裔美国人种族和高度近视有关，这些都会增加青光眼的风险。在理解 ONH 和 PPS 之间的生物力学相互作用方面存在知识差距。哪些 PPS 生物力学特性是最佳的以及如何修改 PPS 以减轻 IOP 引起的 ONH 的机械损伤仍然知之甚少，我们建议使用高分辨率超声。弹性成像技术可通过完整组织解决 ONH 和 PPS 的复杂机械响应厚度，并开始填补知识空白，我们将量化 ONH 和 PPS。正常人类供体眼睛、经过 PPS 重塑的眼睛以及经过实验修改的眼睛的变形我们还将进一步开发这种技术，用于 ONH 和 PPS 的体内生物力学成像。具体来说，我们提出以下目标：1）测试 ONH 变形的预测。与 PPS 变形相关，并且在老年人和非裔美国人种中存在差异，2）测试预测通过PPS重构，ONH变形在眼睛中是不同的，3）测试ONH变形的预测 PPS 生化硬化或软化后发生改变，4) 测试体内 ONH 和 PPS 的可行性猪模型中的超声弹性成像的成功完成将建立一个明确的研究。了解 ONH 和 PPS 之间的生物力学相互作用，这是影响个体眼睛视力的关键因素结合体内生物力学成像技术的发展，这些知识将为减少青光眼视力丧失的新型诊断和治疗策略奠定基础。