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: 8244491
• 负责人: DONALD J BROWN
• 金额: $ 36.72万
• 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/8244491
• 关键词: 3-Dimensional; Accounting; Acoustics; Affect; Age; Aging; 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; regional difference; response; second harmonic; three dimensional structure; tomography; two-photon

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.

原发性开角型青光眼（POAG）是一个严重的和日益增长的健康问题会计 约占全球失明人数的12%研究已经确定了年龄，祖先群体（种族背景）和内部- 眼压（IOP）是POAG发生和进展的重要危险因素。我们长久以来- 范围目标是了解这些已确定的风险因素与相应损失之间的关系 视网膜神经节细胞的分裂目前的观点认为， 视神经乳头（ONH）和筛板（LC）的性质在确定视神经乳头（ONH）和筛板（LC）的位置中起关键作用。 POAG的病理学在初步研究中，我们已经确定了LC的易受 水肿性改变（下、上级）胶原含量较少，显示更多压力诱导 与LC的其他区域（鼻侧和颞侧）相比，变形（更柔顺）。在这些发现的基础上， 该建议的目的是通过以下方式定义ONH的三维生物力学特性： 显微镜下重建LC的结构成分和生物力学特性， 微米尺度，并将这些属性与POAG的危险因素。 基于我们的初步研究，我们提出了以下可检验的假设：1）有 LC的结构和压力引起的变形的区域差异， 易受早期青光眼变化影响的患者胶原蛋白减少，变形增加; 2） LC结构和压力引起的变形的区域差异随着年龄的增加而增加， 祖先群体，例如年龄较大的个体和祖先更容易患POAG的人将有 构造变化较大，表现出较大的压致变形; 3）区域差异 LC结构和压力引起的变形与三维差异直接相关， 微观弹性模量，使得LC的区域最易受昏迷性损伤（和 与年龄和血统相关）与其他材料相比， 地区 为了验证这些假设，我们开发了创新的、最先进的技术， 评估具有高密度的人ONH的三维（3D）结构和生物力学特性。 分辨率这些技术利用了已知的非线性光学效应，该非线性光学效应在高折射率时发生。 由超快激光器产生的高强度光子与组织相互作用。 使用这些新技术，我们建议研究离体正常人的眼睛 和不同年龄的不同祖先通过以下具体目的：1）动态映射4维 (time和空间）IOP诱导的离体人ONH中胶原纤维和弹性纤维结构的变化 使用人工压力室和超快激光; 2）三维重建ONH， 高分辨率（横向0.9 mm，轴向2 mm），可对结构的区域变化进行体积测量 并将这些与测量的压力引起的同一只眼睛中的变形相关; 3）测量区域压力引起的变形。 （上级与下级等）离体人ONH的生物力学性质，以将结构与 生物力学特性和对POAG的敏感性。 我们希望这些调查将提供新的和至关重要的信息， 人类ONH的生物力学特性，并提供了一个更清楚的了解的风险因素， POAG。