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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.

项目总结/文摘