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

• 批准号: 10706958
• 负责人: JUN LIU
• 金额: $ 32.54万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 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/10706958
• 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; Length; Measurement; Measures; Mechanical Stress; Mechanics; Modification; Modulus; Myopia; Optic Disk; Optic Nerve; Optical Coherence Tomography; Papillary; 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; collagenase; combat; computer studies; diagnostic strategy; elastography; feasibility testing; genipin; human old age (65+); imaging modality; in vivo; innovation; modifiable risk; nerve damage; neural; novel; novel diagnostics; novel therapeutic intervention; optic nerve disorder; optical imaging; porcine model; power analysis; radio frequency; response; retinal imaging; submicron; success; treatment effect; treatment group; treatment response; treatment strategy; ultrasound

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.

项目摘要/摘要 青光眼影响了大约300万美国人，并且是全球失明的主要原因。患者 患有进行性视神经病，为此，眼内压（IOP）诱导机械损伤 视神经头（ONH）起着核心作用。当前的治疗均旨在降低IOP。虽然这些治疗是 有益的是，许多患者继续因持续的视神经损伤而失去视力。非常需要 确定其他可修改的危险因素，基于哪些新型治疗方法可以与这一公众作斗争 健康问题。从生物力学上讲，IOP诱导的机械感染水平（即应力和菌株） ONH并非仅由IOP确定。计算研究表明，乳腺周围巩膜（PPS） 模量和厚度是最具影响力的因素之一。有趣的是，PPS生物力学变化是 在年龄较大的非裔美国人种族和高近视中实施，这增加了青光眼风险。然而， 了解ONH和PPS之间的生物力学相互作用存在知识差距。例如， 哪些PPS生物力学特性是最佳的，以及如何修改PPS以减轻IOP诱导 ONH的机械侮辱仍然知之甚少。我们建议使用高分辨率超声 通过完整的组织解决弹性技术以解决ONH和PPS的复杂机械响应 厚度，并开始填补知识差距。使用此技术，我们将量化ONH和PPS 正常人的供体眼中的变形，PPS重塑的供体和实验性修饰的变形 PPS属性。我们还将进一步开发这种技术，用于ONH的体内生物力学成像 动物模型中的PPS。具体而言，我们提出以下目的：1）测试ONH变形的预测 与PPS变形相关，在老年和非裔美国人种族中不同，2）测试预测 PPS重塑的眼睛中的ONH变形不同，3）测试ONH变形为 PPS生化僵硬或软化后改变，4）测试体内和PPS的可行性 猪模型中的超声弹性图。拟议研究的成功完成将建立一个明确的 了解ONH和PPS之间的生物力学相互作用，这是单个眼睛的关键因素 机械敏感性对IOP。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。