The impact of age-related vitreous degeneration and vitreous replacement on scleral biomechanics: a novel mechanism and treatment target for glaucoma

摘要 背景：青光眼是世界范围内导致失明的主要原因。而潜在的 青光眼损伤的机制尚不完全清楚，显然，青光眼的发病率 青光眼随着年龄和眼压的增加而增加。几种生物力学研究 已经表明巩膜是视神经生物力学反应的重要媒介。 神经头(ONH)对眼压的变化，显示出明显的进行性僵硬，随着年龄的增长 ONH(乳头周围巩膜)周围最易受青光眼损伤的区域。而当 先前的研究已经为眼压、脑脊液压力、 血压，以及ONH和筛板的结构硬度，作为决定因素 ONH的机械环境，玻璃体液的作用，填充了ONH之间的空间- 视网膜和晶状体，仍然没有被作为ONH环境的一部分进行调查。 值得注意的是，随着年龄的增长，玻璃体经历了进行性的结构退化。 在整个生命过程中，液体的增加和凝胶体积的减少会削弱其粘弹性 属性。因此，我们提出这种年龄相关性的玻璃体变性沿巩膜 僵硬是ONH生物力学的决定性因素。本研究的目的是：1)确定 玻璃体在动态眼压时调节巩膜生物力学反应中的作用 人类供体眼的变异；2)确定巩膜反应如何在生物力学上 用仿生设计的水凝胶进行了改进。设计：在一组20只人类供体眼球中 在40岁时，我们将测量巩膜在生理性眼压变化过程中的反应 前房。我们将比较四种玻璃体状态下的巩膜生物力学。 腔：i)使用天然玻璃体，ii)用生理盐水替换玻璃体的液体部分后， Iii)在用生理盐水替换剩余的玻璃体凝胶之后，iv)和用 仿生水凝胶旨在匹配年轻玻璃体的粘弹性特性。影响： 阐明巩膜和玻璃体之间复杂的力学关系不仅 提示和改进青光眼的机制模型，它也将提供一个潜在的翻译 开发新的方法来减轻动力引起的机械损伤的机制 ONH的眼压变化。这个项目将是第一个定义这种关系的项目，填补了一个科学 差距。基于ONH-巩膜反应的玻璃体置换术可在临床上进一步探索 基于本文获得的数据的纵向研究和动物模型。 。

Abstract Background: Glaucoma is a leading cause of blindness worldwide. While the potential mechanisms of glaucomatous injury are incompletely understood, it is clear that the incidence of glaucoma increases with age and with intraocular pressure (IOP). Several biomechanical studies have indicated that the sclera is a critical mediator of the biomechanical response of the optic nerve head (ONH) to changes in IOP, showing a significant progressive stiffening with aging in the regions around the ONH (peripapillary sclera) most susceptible to glaucomatous injury. While prior studies have provided valuable insight into the role of IOP, cerebrospinal fluid pressure, blood pressure, and structural stiffness of the ONH and lamina cribrosa , as determinants of the ONH‘s mechanical environment, the role of the vitreous humor, filling the space between ONH- retina and lens, has still not been investigated as being part of the ONH’s environment. Significantly, the vitreous undergoes progressive structural degeneration with aging showing increasing liquid and decreasing gel volumes throughout life that impairs its viscoelastic properties. We therefore propose that such an age-related vitreous degeneration along scleral stiffening is determinant to ONH biomechanics. The Objectives of this study are: 1) to determine the impact of vitreous in modulating the biomechanical scleral response during dynamic IOP variations in human donor eyes; 2) To determine how scleral response can be biomechanically improved with a biomimetic designed hydrogel. Design: In a group of 20 human donor eyes over age of 40, we will measure the sclera’s response during physiological IOP variations induced in the anterior chamber. We will compare the scleral biomechanics in four conditions of the vitreous chamber: i) with the natural vitreous, ii) after replacing the liquid part of the vitreous with saline, iii) after replacing the remaining vitreous gel with saline, iv) and after replacement with a biomimetic hydrogel designed to match the viscoelastic properties of young vitreous. Impact: Elucidating the complex mechanical relationship between the sclera and vitreous will not only inform and improve mechanistic models of glaucoma, it will also provide a potential translational mechanism to develop novel approaches to attenuate the mechanical insult caused by dynamic IOP variations on the ONH. This project will be the first to define this relationship, filling a scientific gap. Vitreous replacement based on the ONH-sclera response can be further explored in clinical longitudinal studies and animal models based on the data obtained herein. .