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

基本信息

批准号：
8703108
负责人：
Jonathan Pieter Vande Geest
金额：
$ 36.26万
依托单位：
UNIVERSITY OF ARIZONA
依托单位国家：
美国
项目类别：
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/8703108
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 Geometry 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

项目摘要

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.

项目概要青光眼是全球第二大失明原因，有 700 万人因此失明。大量研究表明，原发性开角型青光眼 (POAG) 的发病率较高。非洲裔和西班牙裔人群中的患病率。青光眼的机械理论假设作用于视神经的机械损伤力导致视网膜丧失神经节细胞功能。虽然有证据表明筛板 (LC) 的细胞外基质和青光眼存在时视乳头周围巩膜（PS）重塑，但这种重塑尚未广泛在某些高风险人群（老年人、非洲人后裔 (AD)、西班牙裔 (HE)）中进行量化。优惠这些群体的 PS 微观结构和机械性能的差异可能提供了一种机制 POAG 可以在正常 IOP 下发生。当前的研究计划将调查这种关系 PS 和 LC 基体微观结构和机械性能之间的关系，试图确定这些关系受到种族/民族和年龄的影响。拟议工作的中心假设是 LC 和 PS 的微观结构和机械性能存在差异，具体取决于以下因素：种族/民族和年龄。假设这些变化在青光眼患病率升高中发挥了作用 AD 和 HE 人群与欧洲血统 (ED) 人群相比，与眼压。虽然之前已经研究过 LC 和 PS 的细胞外基质微观结构，但如何目前尚不清楚这种组织与这些组织的机械功能的关系。这是主要是因为几乎所有微观结构信息的量化都是由依赖于快速冷冻或将组织固定在包埋介质中的组织学研究（从而排除同时机械表征）。我们最近开发了一种微光机械（MOMD）该装置能够同时测量未固定的 LC 和 PS 的基质组织，同时这些组织发生机械变形。 MOMD 激发胶原蛋白的二次谐波产生双光子发射弹性蛋白荧光，同时将眼后组织暴露在平面双轴载荷或压力膨胀载荷。该项目的三个主要目标是找出差异（作为种族/民族和年龄的函数）1) 不同眼压下人类 LC 的微观结构组织； 2) 不同眼压下人体 PS 的生物力学反应和微观结构； 3）生物力学使用基于微观结构的计算模拟来模拟眼后组织的环境。提供一个详细说明了与年龄和种族相关的 LC 和 PS 微观结构和机械差异特性可能为开发新型诊断和治疗提供独特的机会机会。