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：
8188325
负责人：
Jonathan Pieter Vande Geest
金额：
$ 33.68万
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/8188325
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

项目摘要

DESCRIPTION (provided by applicant): 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. PUBLIC HEALTH RELEVANCE: As the second leading cause of blindness worldwide, glaucoma is estimated to affect 60 million people in 2010 and will affect 80 million by 2020. Alterations in the makeup and properties of the tissues near the optic nerve may predispose certain high risk populations to primary open angle glaucoma, even at relatively low intraocular pressures. Identification of such changes may eventually lead to improved diagnosis and treatment of this disease.

描述（由申请人提供）：青光眼是全球失明的第二大主要原因，因为有700万人与这种情况失明。有广泛的研究得出结论，主要的开头青光眼（POAG）在非洲血统和西班牙裔种族的种群中的患病率更高。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神经节细胞功能丧失。虽然有证据表明，在青光眼存在的情况下，椎板纤维状体（LC）和毛皮堆肥巩膜（PS）重塑的细胞外基质尚未在某些较高的风险群体（年龄，非洲后裔（AD），西班牙族裔族裔（HE）中进行广泛量化。这些人群的PS微结构和机械性能的优先差异可能会提供一种机制，可以在正常的IOPS下发生POAG。当前的研究建议将研究PS和LC矩阵微观结构与机械性能之间的关系，以寻求确定这些关系如何受到种族/种族和年龄的影响。拟议工作的中心假设是，LC和PS的微观结构和机械性能的差异是种族/民族和年龄的函数。假设这些变化在AD人群中青光眼的较高患病率中起作用，与欧洲血统相比，他与眼内压力无关的欧洲血统相比。虽然先前已经研究了LC和PS的细胞外基质微观结构，但目前尚不了解该组织与这些组织的机械功能的关系。这主要是由于这一微观结构信息的几乎所有量化都是由组织学研究造成的，这些研究依赖于快速冻结或将组织固定在嵌入培养基中（从而排除同时的机械表征）。我们最近开发了一种微型力学（MOMD）设备，该设备能够同时测量未固定的LC和PS的基质组织，而这些组织经历了机械变形。 MOMD激发了第二次谐波产生的胶原蛋白和两光子发射的弹性弹性弹性弹性弹性，同时将眼后组织暴露于平面双轴或压力通气载荷上。该项目的三个主要目的是确定1）各种IOPS人类LC的微观结构组织的差异（作为种族/种族和年龄的函数）； 2）生物力学响应和微观结构在各种IOPS上的人类PS； 3）使用基于微观结构的计算模拟的后眼组织的生物力学环境。提供有关年龄和种族相关的LC和PS微结构和机械性能的详细说明，可以为开发新的诊断和治疗机会提供独特的机会。公共卫生相关性：作为全球失明的第二大主要原因，青光眼估计在2010年会影响6000万人，到2020年将影响8000万人。在视神经附近的构成和特性的改变可能会使某些高风险群体更容易受到一定的高风险群体，即使在相对低的核内压力下，也可能会使原发性的开放角度glaucoma更加易受。这种变化的鉴定最终可能导致改善该疾病的诊断和治疗。