Extracelluar Matrix Organization and Biomechanics of the Lamina Cribrosa and Peri

筛板和周周的细胞外基质组织和生物力学

• 批准号: 8509699
• 负责人: Jonathan Pieter Vande Geest
• 金额: $ 35.17万
• 依托单位: UNIVERSITY OF ARIZONA
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-01 至 2016-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8509699
• 关键词: Accounting; Affect; African; African race; Age; Aging; Axon; Behavior; Biomechanics; Blindness; Blood Vessels; Cell physiology; Clinical Research; Collagen; Computer Simulation; Connective Tissue; Data; Development; Devices; Diagnosis; Disease; Economic Inflation; Elastin; Environment; Ethnic Origin; Ethnic group; European; Extracellular Matrix; Fiber; Finite Element Analysis; Fluorescence; Freezing; Generations; Glaucoma; Goals; High Prevalence; Hispanics; Human; Image; Inferior; Injury; Lead; Least-Squares Analysis; Maps; Measures; Mechanics; Microscope; Minority Groups; Modeling; Nose; Ocular Hypertension; Optic Disk; Optic Nerve; Optic Nerve Injuries; Patients; Physiologic Intraocular Pressure; Physiological; Play; Population; Populations at Risk; Porosity; Predisposition; Primary Open Angle Glaucoma; Procedures; Property; Race; Research Proposals; Rest; Retinal Ganglion Cells; Risk; Risk Factors; Role; Sclera; Stress; Techniques; Testing; Thick; Tissue Donors; Tissues; Visually Impaired Persons; Weight-Bearing state; Work; aged; base; comparison group; high risk; improved; light scattering; novel; optic nerve disorder; pressure; prospective; response; second harmonic; theories; tissue fixing; two-photon

Project Summary Glaucoma is the 2nd leading cause of blindness worldwide, as 7 million people are blind from this condition. There have been extensive studies concluding that primary open angle glaucoma (POAG) has a higher prevalence in populations of both African descent and Hispanic ethnicity. The mechanical theory of glaucoma rests on the assumption that mechanical damage forces acting on the optic nerve cause a loss of retinal ganglion cell function. While there is evidence that the extracellular matrix of the lamina cribrosa (LC) and peripapillary sclera (PS) remodel in the presence of glaucoma, this remodeling has not been extensively quantified in certain higher risk populations (aged, African Descent (AD), Hispanic Ethnicity (HE)). Preferential differences in the PS microstructure and mechanical properties of these populations may provide a mechanism by which POAG can occur at normal IOPs. The current research proposal will investigate the relationship between PS and LC matrix microstructure and mechanical properties, seeking to identify how these relationships are affected by race/ethnicity and age. The central hypothesis of the proposed work is that differences in the microstructure and mechanical properties of the LC and PS exist as a function of race/ethnicity and age. These changes are hypothesized to play a role in the higher prevalence of glaucoma in populations of AD and HE compared with those of European Descent (ED), independent of the level of intraocular pressure. While the extracellular matrix microstructures of the LC and PS have been investigated previously, how such organization relates to the mechanical function of these tissues is not currently understood. This is primarily due to the fact that nearly all quantification of this microstructural information has resulted from histological studies which rely on snap freezing or fixing the tissue in an embedding medium (thus precluding simultaneous mechanical characterization). We have recently developed a micro-optomechanical (MOMD) device which is capable of simultaneously measuring the matrix organization of unfixed LC and PS while these tissues undergo mechanical deformations. The MOMD excites the second harmonic generation of collagen and the two-photon emitted fluorescence of elastin while simultaneously exposing posterior ocular tissues to either planar biaxial or pressure-inflation loads. The three primary aims of this project are to identify differences (as a function of race/ethnicity and age) in 1) the microstructural organization of the human LC at various IOPs; 2) the biomechanical response and microstructure the human PS at various IOPs; and 3) the biomechanical environment of posterior ocular tissues using microstructurally-based computational simulations. Providing a detailed account of age and ethnicity associated differences in LC and PS microstructure and mechanical properties may provide a unique opportunity for the development of novel diagnosis and treatment opportunities.

项目摘要 青光眼是全世界失明的第二大主要原因，因为700万人对这种情况失明。 已经有广泛的研究得出结论，主要的开角青光眼（POAG）具有较高的 非洲血统和西班牙种族的人口普遍存在。青光眼的机械理论 基于这样的假设，即作用在视神经上的机械损伤力会导致视网膜丧失 神经节细胞功能。虽然有证据表明lamina cribrosa（LC）的细胞外基质和 在青光眼存在的情况下，乳头状巩膜（PS）重塑，这种重塑尚未广泛 在某些较高的风险人群（年龄，非洲血统（AD），西班牙裔种族（HE）中进行量化。优惠 这些人群的PS微结构和机械性能的差异可能会提供机制 POAG可以在正常的IOPS下发生。当前的研究建议将调查关系 在PS和LC矩阵微结构和机械性能之间，试图确定这些方式 人际关系受到种族/种族和年龄的影响。拟议工作的中心假设是 LC和PS的微结构和机械性能的差异是存在的函数 种族/种族和年龄。假设这些变化在青光眼的较高流行率中发挥作用 与欧洲血统相比，AD的种群（ED）与之相比 眼压。 虽然先前已经研究了LC和PS的细胞外基质微观结构，但如何 当前尚不了解这种组织与这些组织的机械功能有关。这是 主要是由于以下事实：该微观结构信息的几乎所有量化都是由 依赖于冻结或固定组织在嵌入培养基中的组织学研究（因此排除 同时机械表征）。我们最近开发了一种微型力学（MOMD） 能够同时测量未固定LC和PS的矩阵组织的设备 组织发生机械变形。 MOMD激发了第二次谐波胶原蛋白 两光子发出的弹性荧光同时将眼组织暴露于 平面双轴或压力通气负荷。该项目的三个主要目的是确定差异 （作为种族/种族和年龄的函数）在1）各种IOPS的人体LC的微观结构组织； 2）生物力学响应和微观结构在各种IOPS上的人类PS； 3）生物力学 使用基于微观结构的计算模拟的眼部组织环境。提供 年龄和种族与LC和PS微观结构以及机械差异相关的详细说明 特性可能为开发新的诊断和治疗提供独特的机会 机会。