The Biomechanics of the Human Posterior Sclera: Effects of Age, Sex, and Glaucoma

描述（由申请人提供）：青光眼是美国致盲的主要原因，也是全球第二大致盲原因。人们一致认为，眼压水平在眼组织中产生生物力学反应，这是青光眼损伤早期事件的基础。IOP通过后巩膜的反应转化为视神经头的机械应力，视神经头是后巩膜的一个开口，用于视网膜神经节细胞（RGC）进入大脑。这会导致RGC轴突、胶质细胞和滋养毛细血管的变形。在视神经头部，RGC轴突轴突运输的阻断导致了它们的最终死亡。因此，视神经头巩膜的物理相互作用是青光眼视神经病变发展的核心。提高这些结构的力学行为的知识将促进对青光眼损伤的理解，其早期诊断和预防由该疾病引起的失明。该提案的目标是(1)测量区域变化的厚度、胶原蛋白和弹性蛋白结构的各向异性、IOP波动时的膨胀反应和人类后巩膜的粘弹性特性，比较年龄、性别、青光眼损伤严重程度的影响，以及各种酶和胶原交联剂的影响。(2)模拟测量的巩膜粘弹性和结构变化对ONH对IOP动态波动的响应的影响。开角型青光眼的粘弹性和结构可能与正常眼不同。这些又可能随着青光眼损伤的进展而改变。青光眼和正常眼睛在生理或解剖特征上的差异将为改进诊断测试提供候选基因，以及适用于新治疗方法的转译后过程和途径。我们将开始探索通过胶原交联硬化巩膜和酶降解软化巩膜来改变巩膜粘弹性行为的治疗方法的发展。

DESCRIPTION (provided by applicant): Glaucoma is a leading cause of blindness in the United States, and the second leading cause worldwide. There is consensus that the level of IOP generates a biomechanical response in the ocular tissues that is fundamental to the early events in glaucoma damage. The IOP is translated into mechanical stresses on the optic nerve head, an opening in the posterior sclera for the passage of retinal ganglion cells (RGC) to the brain, by the response of the posterior sclera. This causes deformation of the RGC axons, glia, and nourishing capillaries. At the optic nerve head, it is well established that blockade of axonal transport in RGC axons leads to their ultimate death. Thus, the physical interaction of the sclera at the optic nerve head is central to the development of glaucomatous optic neuropathy. Improved knowledge of the mechanical behavior of these structures will advance understanding of glaucoma injury, its early diagnosis, and prevention of the blindness caused by the disorder. The goals of the proposal are to (1) measure the regionally varying thickness, anisotropy of the collagen and elastin structure, the inflation response to IOP fluctuations, and viscoelastic properties of the posterior human sclera, comparing for the effects of age, sex, severity of glaucoma damage, and effects of various enzymatic and collagen cross linking agents, and (2) model the effects of the measured variations in scleral viscoelastic properties and structure on the response of the ONH to dynamic fluctuations in IOP. It is likely that the viscoelastic properties and structure of human eyes with open angle glaucoma differ from those of normal eyes. These are in turn likely altered by the progression of glaucoma damage. Differences between glaucoma and normal eyes in their physiological or anatomical features will suggest candidate genes for improved diagnostic testing, as well as post-translational processes and pathways that would be amenable to new therapeutic approaches. We will begin to explore the development of therapeutic approaches that alter the viscoelastic behavior of the sclera by collagen cross linking to stiffen the sclera and enzymatic degradation of soften the sclera. PUBLIC HEALTH RELEVANCE: Glaucoma is a leading cause of blindness in the United States, and the second leading cause worldwide. The implications of this work can be important to understanding the susceptibility of individuals to glaucoma. We can envision the development of non-invasive testing procedures, that for example measure a key mechanical property of the sclera, to identify individuals at risk and determine their degree of susceptibility based on the biomechanical properties of their eyes.