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

年龄相关性玻璃体变性和玻璃体置换对巩膜生物力学的影响：青光眼的新机制和治疗目标

• 批准号: 10647522
• 负责人: Gianfranco Bianco
• 金额: $ 23.91万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10647522
• 关键词: Age; Aging; Animal Model; Attenuated; Behavior; Biomechanics; Biomimetics; Blindness; Blood Pressure; Center Core Grants; Cerebrospinal Fluid Pressure; Characteristics; Clinical; Complex; Core Grant; Craniocerebral Trauma; Data; Device Designs; Environment; Eye; Frequencies; Gel; Glaucoma; Human; Hydrogels; Impairment; Incidence; Infusion procedures; Injury; Life; Liquid substance; Longitudinal Studies; Measurement; Measures; Mechanical Stress; Mechanics; Mediator; Methods; Modeling; Optic Disk; Papillary; Periodicity; Phase; Physiologic Intraocular Pressure; Physiological; Pilot Projects; Predisposition; Property; Publishing; Retina; Role; Saline; Sampling; Sclera; Stress; Study models; System; Testing; Variant; Vitreous Chamber; Vitreous humor; absorption; age related; anterior chamber; design; human data; improved; insight; lens; novel; novel strategies; response; sensor; translational potential; transmission process; viscoelasticity

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. .

摘要 背景：青光眼是世界范围内致盲的主要原因。而潜在的 昏迷性损伤的机制还不完全清楚，很明显， 青光眼随着年龄和眼内压（IOP）而增加。几项生物力学研究 已经表明巩膜是光学部的生物力学响应的关键介质 神经乳头（ONH）对IOP变化的影响，显示随着年龄的增长， ONH（视乳头周围巩膜）周围的区域最容易发生青光眼损伤。而 先前的研究提供了对IOP，脑脊液压力， 血压，ONH和筛板的结构刚度，作为 ONH的机械环境，玻璃体液的作用，填补ONH之间的空间- 视网膜和透镜作为ONH环境的一部分尚未被研究。 值得注意的是，随着年龄的增长，玻璃体经历进行性结构退化， 在整个寿命期间增加液体和减少凝胶体积， 特性.因此，我们认为这种年龄相关的玻璃体变性沿着巩膜 硬化是ONH生物力学的决定性因素。本研究的目的是：1）确定 玻璃体在动态眼压下调节巩膜生物力学反应中的作用 2）为了确定巩膜反应如何可以生物力学地 用仿生设计的水凝胶改进。设计：在一组20只人类供体眼中， 40岁时，我们将测量巩膜在生理性IOP变化期间的反应， 前房我们将比较四种玻璃体状态下的巩膜生物力学 腔室：i）用天然玻璃体，ii）在用盐水替换玻璃体的液体部分之后， iii）用盐水替换剩余的玻璃体凝胶后， 仿生水凝胶设计为匹配年轻玻璃体的粘弹性。影响： 阐明巩膜和玻璃体之间复杂的力学关系不仅 提供信息和改进青光眼的机理模型，它也将提供潜在的翻译 开发新的方法来减弱由动态引起的机械损伤的机制 ONH的IOP变化。这个项目将是第一个定义这种关系，填补了科学的 间隙基于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。 .