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. .

抽象的 背景：青光眼是全球范围内导致失明的主要原因。 青光眼损伤的机制尚不完全清楚，但很明显，青光眼的发生率 青光眼随着年龄和眼压 (IOP) 的增加而增加。 已经表明巩膜是视神经生物力学反应的关键调节者 神经乳头（ONH）与眼压的变化有关，随着年龄的增长，显示出明显的渐进性僵硬 ONH（视乳头周围巩膜）周围的区域最容易受到青光眼损伤。 先前的研究对眼压、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，填充了ONH-之间的空间 视网膜和晶状体尚未作为 ONH 环境的一部分进行调查。 值得注意的是，玻璃体经历进行性结构退化，并显示出老化现象 在整个生命周期中增加液体并减少凝胶体积，从而损害其粘弹性 因此，我们提出这种与年龄相关的巩膜玻璃体变性。 硬化是 ONH 生物力学的决定因素。本研究的目的是：1) 确定。 动态眼压期间玻璃体对调节巩膜生物力学反应的影响 人类捐赠者眼睛的差异；2) 确定巩膜反应如何进行生物力学 通过仿生设计的水凝胶进行改进 设计：在 20 多个人类捐赠者的眼睛中进行。 40岁时，我们将测量巩膜在生理眼压变化期间的反应 我们将比较四种玻璃体情况下的巩膜生物力学。 腔室：i) 使用天然玻璃体，ii) 用盐水替换玻璃体的液体部分后， iii) 用盐水替换剩余的玻璃体凝胶后，iv) 并用 仿生水凝胶旨在匹配年轻玻璃体的粘弹性特性。 阐明巩膜和玻璃体之间复杂的力学关系不仅将 告知并改进青光眼的机制模型，它还将提供潜在的转化 机制开发新方法来减轻动态引起的机械损伤 ONH 上的 IOP 变化 该项目将首次定义这种关系，填补了科学空白。 基于 ONH 巩膜反应的玻璃体置换术可以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。 。