Structure and Biomechanics of the Human Optic Nerve Head

原发性开角型青光眼(POAG)是一个严重且日益严重的健康问题 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发生发展的重要危险因素。我们的长- 范围目标是了解这些已建立的风险因素与应答性损失之间的关系 视网膜神经节细胞是这种疾病的特征。目前的智慧认为，生物力学 视神经头(ONH)和筛板(LC)的性质在确定 开角型青光眼的病理学在初步研究中，我们已经确定了LC的易感区域 青光眼改变(下、上)含有较少的胶原，表现为更多的压力诱导 与LC的其他区域(鼻部和颞部)相比，变形(更顺应)。基于这些发现， 这项建议的目的是通过以下方式定义ONH的三维生物力学特性 显微重建横跨LC的结构成分和生物力学特性 Micron评估这些特性，并将其与POAG风险因素相关联。 基于我们的初步研究，我们提出了以下可检验的假设：1)存在 液晶结构和压力引起的变形的区域差异使得区域 容易早期青光眼改变的胶原减少和变形增加；2) 液晶结构和压力变形的区域差异随着年龄的增加而增大，并随年龄的变化而变化 祖先群体，这样年长的个体和那些祖先更容易患POAG的人将会有 较大的构造变化和较大的压力引起的变形；3)认为地区差异 液晶的结构和压力引起的变形与三维空间的差异直接相关， 微观弹性模数，使得LC最容易受到青光眼损害的区域(和 与年龄和血统有关)的弹性模数与其他 地区。 为了验证这些假设，我们开发了创新的尖端技术，以在全球范围内 评价人高位ONH的三维结构和生物力学特性 决议。这些技术利用了已知的非线性光学效应，当高电平 超快激光产生的强度光子与组织相互作用。 利用这些新技术，我们计划研究正常人的体外人眼。 和不同年龄的不同祖先通过以下具体目标：1)在4个维度上动态映射 (时间和空间)眼压诱导的体外人ONH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)ONH的三维重建 高分辨率(横向0.9毫米，纵向2毫米)，以体积测量区域结构的变化 并将这些与测量到的压力引起的同一只眼变形联系起来；3)测量区域 (上级与下级等)离体人ONH的生物力学特性与关节结构的关系 生物力学特性和对POAG的易感性。 我们期望，这些调查将提供有关以下方面的新的、至关重要的信息 人类ONH的生物力学特性，有助于更清楚地了解ONH的危险因素 普阿格。

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.