Structure and Biomechanics of the Human Optic Nerve Head

人类视神经头的结构和生物力学

• 批准号: 7887791
• 负责人: DONALD J BROWN
• 金额: $ 36.93万
• 依托单位: UNIVERSITY OF CALIFORNIA-IRVINE
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2014-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7887791
• 关键词: 3-Dimensional; Accounting; Acoustics; Affect; Age; Aging; Arts; Biomechanics; Blindness; Collagen; Collagen Fibril; Coupled; Data; Development; Dimensions; Disease; Elastic Fiber; Elasticity; Elastin; Eye; Fluorescence; Functional disorder; Generations; Glaucoma; Goals; Health; Human; Individual; Inferior; Injury; Investigation; Lasers; Lateral; Lead; Maps; Measurement; Measures; Microscope; Microscopic; Microscopy; Monitor; Nose; Optic Disk; Optics; Pathology; Photons; Play; Predisposition; Primary Open Angle Glaucoma; Property; Public Health; Race; Radiation; Research Personnel; Resolution; Retinal Ganglion Cells; Risk Factors; Role; Signal Transduction; Structure; Technology; Testing; Time; Tissues; Ultrasonography; base; innovation; multidisciplinary; new technology; novel; pressure; public health relevance; regional difference; response; second harmonic; three dimensional structure; tomography; two-photon

DESCRIPTION (provided by applicant): Primary open angle glaucoma (POAG) represents a serious and growing health problem accounting for ~12% of global blindness. Studies have identified age, ancestral group (racial background), and intra- ocular pressure (IOP) as significant risk factors for the development and progression of POAG. Our long- range goal is to understand the relationship between these established risk factors and the responsive loss of retinal ganglia cells that characterizes this disease. Current wisdom proposes that the biomechanical properties of the optic nerve head (ONH) and lamina cribrosa (LC) play a critical role in defining the pathology of POAG. In preliminary studies, we have identified that regions of the LC susceptible to glaucomatous change (inferior, superior) contain less collagen and show more pressure-induced deformation (more compliant) than other regions of the LC (nasal and temporal). Building on these findings, the objective of this proposal is to define the 3 dimensional biomechanical properties of the ONH by microscopically reconstructing the structural components and biomechanical properties across the LC at a micron scale and relate these properties to POAG risk factors. Based on our preliminary studies we propose the following testable hypotheses:1) That there are regional differences in both the structure and pressure-induced deformation of the LC such that regions susceptible to early glaucomatous change have decreased collagen and increased deformation; 2) That the regional differences in LC structure and pressure-induced deformation increase with age and vary with ancestral group, such that older individuals and those with ancestries more susceptible to POAG will have greater structural changes and show greater pressure induced deformation; 3) That the regional differences in LC structure and pressure-induced deformation are directly related to differences in the 3 dimensional, microscopic elastic modulus such that regions of the LC most susceptible to glaucomatous damage (and related to age and ancestry) will have significant differences in the elastic modulus compared to other regions. To test these hypotheses, we have developed innovative, state of the art technologies to globally assess the three dimensional (3D) structure and biomechanical properties of the human ONH with high resolution. These technologies take advantage of known non-linear optical affects that occur when high intensity photons generated by ultrafast lasers interact with tissue. Using these novel technologies we propose to study ex vivo human eyes from normal individuals and different ancestries at varying ages by the following Specific Aims: 1) Dynamically map in 4 dimensions (time and space) IOP induced changes in collagen fibril and elastic fiber structure in ex vivo human ONH using an artificial pressure chamber and an ultrafast laser; 2) Three dimensionally reconstruct the ONH at high resolution (0.9 mm lateral and 2 mm axial) to volumetrically measure the regional changes in structure and relate these to the measured pressure induce deformations in the same eye; 3) Measure the regional (superior vs. inferior etc.) biomechanical properties of ex vivo human ONH to relate structure to the biomechanical properties and susceptibility to POAG. We expect that these investigations will provide new, and critically important, information concerning the biomechanical properties of the human ONH and provide a clearer understanding of the risk factors for POAG. PUBLIC HEALTH RELEVANCE: In this proposal, we will clarify the role of collagen and elastic components of the lamina cribrosa (LC) in the pathophysiology of axonal injury that occurs with aging and how it may be accelerated by increased IOP. We fully expect these data to lead to critically important information concerning the biomechanical properties of the human optic nerve head (ONH) and provide a clearer understanding of the risk factors for primary open angle glaucoma (POAG). To achieve our goal, we will use innovative, state of the art technologies based on ultrafast lasers that can produce two photon excited fluorescence for identifying elastin, second harmonic generated signals for identifying collagen and laser induced optical breakdown to probe the microscopic biomechanical properties using Acoustic Radiation Force Elastic Microscopy to globally assess the three dimensional structure and biomechanical properties of the ONH.

描述（由申请人提供）：主要的开角青光眼（POAG）代表严重且不断增长的健康问题，占全球失明的约12％。研究已经确定年龄，祖先（种族背景）和眼部压力（IOP）是POAG发展和发展的重要危险因素。我们的长距离目标是了解这些已建立的危险因素与特征这种疾病的视网膜神经节细胞的反应性丧失之间的关系。当前的智慧提出，视神经头（ONH）和lamina cribrosa（LC）的生物力学特性在定义POAG的病理方面起着至关重要的作用。在初步研究中，我们已经确定LC的区域易受青光眼变化（下，上级）的胶原蛋白较少，并且与LC的其他区域相比，压力诱导的变形更大（更顺从）（鼻和时间）。在这些发现的基础上，该提案的目的是通过微观重建LC的结构成分和生物力学特性来定义ONH的3维生物力学特性，并将这些特性与POAG风险因素联系起来。 基于我们的初步研究，我们提出了以下可检验的假设：1）结构和压力诱导的LC变形存在区域差异，使得易感早期青光眼变化的区域降低了胶原蛋白和变形的增加； 2）LC结构的区域差异和压力诱导的变形随着年龄的增长而随着祖先的变化而变化，以使年龄较大的个体和患有POAG更容易受到POAG的祖先的人会有更大的结构变化，并显示出更大的压力诱导的变形； 3）LC结构和压力诱导的变形的区域差异与3维，微观弹性模量的差异直接相关，使得与其他区域相比，LC最容易受到青光眼损伤（并且与年龄和祖先有关）最容易受到青光眼损伤（并且与年龄和祖先有关）的区域将具有显着差异。 为了检验这些假设，我们开发了创新的，最先进的技术，以高分辨率评估人类ONH的三维（3D）结构和生物力学特性。这些技术利用已知的非线性光学影响，当超快速激光器与组织相互作用时，就会发生高强度光子。 使用这些新技术，我们建议通过以下特定目的研究正常个体的离体人眼和不同年龄的不同祖先：1）在4个维度（时间和空间）中动态映射IOP诱导的胶原原纤维和弹性纤维结构的变化，该胶原蛋白纤维和弹性纤维结构使用人工压力室和超级捕集室和超级捕集室和Ultrafast Haserer; 2）三维在高分辨率（0.9 mm侧向和2 mm轴向）下重建ONH，以体积测量结构的区域变化，并将其与所测量的压力相关联导致同一眼睛的变形； 3）测量体内人体ONH的区域（上与下等）生物力学特性，以将结构与生物力学特性和与POAG的敏感性相关联。 我们希望这些调查将提供有关人类ONH生物力学特性的新的，至关重要的信息，并对POAG的危险因素有更清晰的了解。 公共卫生相关性：在这项提案中，我们将阐明椎板纤维状体（LC）的胶原蛋白和弹性成分在随着衰老衰老而发生的轴突损伤的病理生理学中，以及IOP增加如何加速其。我们完全期望这些数据会导致有关人视神经头（ONH）生物力学特性的至关重要的信息，并对主要开放角度青光眼（POAG）的危险因素提供了更清晰的了解。为了实现我们的目标，我们将基于超快激光器使用创新的艺术技术，可以产生两个光子激发荧光，以识别弹性蛋白，第二个谐波生成的信号来识别胶原蛋白和激光诱导的光学分解，以探测微观生物力学特性，使用声辐射弹性弹性弹性弹性弹性弹性弹性，并评估了三个二氧化二氧化胜地。