Biomechanical Interplay between Optic Nerve Head and Peripapillary Sclera

项目总结/摘要 青光眼影响约300万美国人，是全球失明的主要原因。患者 患有进行性视神经病变，其中眼内压（IOP）诱导了眼内动脉的机械损伤。 视神经乳头（optic nerve head，ONH）起着中枢作用。目前的治疗都是为了降低IOP。虽然这些治疗 虽然这种治疗是有益的，但许多患者继续因持续性视神经损伤而丧失视力。非常需要 确定其他可改变的风险因素，在此基础上开发新的治疗方法来对抗这种公众 健康问题。生物力学上，IOP诱导的机械损伤水平（即，应力和应变） ONH不是由IOP单独决定的。计算研究表明，乳头周围巩膜（PPS） 模量和厚度是最有影响的因素。有趣的是，PPS生物力学变化是 与老年、非裔美国人种族和高度近视有关，这些因素增加了青光眼的风险。然而，在这方面， 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。比如说， PPS的生物力学性能最佳，以及如何修改PPS以减轻IOP诱导的 对ONH的机械损伤仍然知之甚少。我们建议使用高分辨率超声波 弹性成像技术，通过全组织解析ONH和PPS的复杂机械反应 厚度，并开始开始填补知识空白。使用这种技术，我们将量化ONH和PPS 正常人供体眼、PPS重塑眼和实验性修改眼的变形 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， PPS在动物模型中。具体而言，我们提出以下目标：1）检验ONH形变的预测 与PPS变形相关，在老年和非洲裔美国人中不同，2）检验预测 PPS重塑眼ONH变形不同，3）测试ONH变形是PPS重塑眼的预测， 在PPS的生化硬化或软化后改变，以及4）测试体内ONH和PPS的可行性 猪模型中的超声弹性成像。成功完成拟议的研究将建立一个明确的 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。 对IOP的机械敏感性。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的诊断和治疗策略奠定基础。

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.