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

描述（由申请人提供）：青光眼是美国的主要致盲原因，也是全球第二大致盲原因。人们一致认为，IOP水平在眼组织中产生生物力学响应，这是青光眼损伤早期事件的基础。通过后巩膜的响应，IOP被转化为视神经头上的机械应力，视神经头是后巩膜中用于视网膜神经节细胞（RGC）通向大脑的通道的开口。这导致RGC轴突、神经胶质和滋养毛细血管变形。在视神经头，已经确定阻断RGC轴突中的轴突运输导致其最终死亡。因此，视神经乳头处巩膜的物理相互作用是青光眼性视神经病变发展的中心。对这些结构的力学行为的进一步了解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。该建议的目标是（1）测量区域变化的厚度、胶原和弹性蛋白结构的各向异性、对IOP波动的膨胀响应、以及人后巩膜的粘弹性，比较年龄、性别、青光眼损伤的严重性的影响、以及各种酶和胶原交联剂的影响，以及（2）模拟巩膜粘弹性和结构的测量变化对ONH对IOP动态波动的响应的影响。开角型青光眼患者眼的粘弹性和结构可能与正常眼不同。这些反过来可能会随着青光眼损害的进展而改变。青光眼和正常眼睛在生理或解剖特征上的差异将提示用于改进诊断测试的候选基因，以及可用于新治疗方法的翻译后过程和途径。我们将开始探索通过胶原交联以包裹巩膜和酶降解软化巩膜来改变巩膜的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.