Relating Structure to Function in Optic Neuropathies

视神经病变的结构与功能的关系

• 批准号: 10334429
• 负责人: Nimesh Bhikhu Patel
• 金额: $ 37.1万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-01-01 至 2023-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10334429
• 关键词: 3-Dimensional; Acute; Affect; Age; Agreement; Anatomy; Appearance; Area; Autopsy; Axon; Basic Science; Blindness; Cell Density; Characteristics; Clinical; Clinical Research; Cornea; Data; Diagnosis; Disease; Disease Management; Disease Progression; Electroretinography; Epidemiology; Extracellular Matrix; Eye; Face; Family; Functional disorder; Glaucoma; Goals; Healthcare; Histologic; Image; Immunohistochemistry; Individual; Individual Differences; Inner Plexiform Layer; Investigation; Knowledge; Lead; Left; Location; Longitudinal Studies; Measures; Methods; Modeling; Monitor; Monkeys; Neuroglia; Neuropathy; Optic Disk; Optical Coherence Tomography; Outcome; Pathologic; Pathology; Patients; Perimetry; Pharmacology; Physiologic Intraocular Pressure; Population; Population Distributions; Predisposition; Prevalence; Public Health; Race; Recording of previous events; Retina; Retinal Ganglion Cells; Risk; Sampling; Scanning; Scanning Electron Microscopy; Stimulus; Structure; Technology; Testing; Thick; Thinness; Tissues; United States; Vision; base; blind; clinical practice; density; design; diagnostic technologies; disorder risk; experimental study; ganglion cell; histological studies; improved; in vivo; non-invasive imaging; nonhuman primate; optic nerve disorder; predictive modeling; relating to nervous system; response; retinal damage; retinal nerve fiber layer; visual threshold

DESCRIPTION Glaucoma is a group of diseases that results in a pathological loss of retinal ganglion cells (RGC) and irreversible vision loss. Although glaucoma is an optic neuropathy with characteristic optic nerve head (ONH) changes, risk of developing disease is not based on ONH structure, but factors including intraocular pressure (IOP), central corneal thickness, age, race and family history. In early disease, there is significant thinning of the optic nerve head (ONH) rim tissue that precedes RGC loss. We hypothesize that the early thinning of the ONH neuroretinal rim tissue (NRR) is related to changes in the glia and extracellular matrix, but not axonal content, which we will investigate using immunohistochemistry and 3D serial block-face scanning electron microscopy in the non- human primate experimental glaucoma model. We also hypothesize that the ONH NRR response to transient changes in IOP is a reflection of the NRR tissue composition, and predictive of the rate of RGC loss (SA1). Clinically, RGC content of the eye is assessed with non-invasive imaging using optical coherence tomography (OCT), for structure, and visual thresholds, for function. OCT structural measures have low variability and have revolutionized how glaucoma is assessed. However, the RGC correspondence to OCT measures is not known, and cannot be estimated from in vivo measures. In fact, the linear relationship for all OCT derived RGC measures is not correct. In SA2, the relationship between OCT derived measures of the circumpapillary retinal nerve fiber layer and ganglion cell inner plexiform thickness will be related to RGC content at all stages of neuropathy using rigorous histological methods. The goal of this aim is develop methods to estimate RGC content in the eye. For a disease that results in irreversible vision loss, it is important that visual function is also assessed accurately. In principal there should also be excellent correspondence between RGC content estimates from OCT measures and that from visual thresholds. Because structural measures are objective and less variable, it would be ideal to accurately predict vision using structural measures. However there is significant discrepancy between structural and functional measures. Some of the reasons for this disjunction is that visual function tests do not use appropriate spatial sampling and stimulus size. In these experiments we will investigate the relationship between RGC content and visual thresholds using higher spatial density and varying stimulus sizes (SA3). Our goal is to establish robust methods to predict visual function based on non-invasive structural imaging. Overall, these studies are designed to improve our understanding of disease pathophysiology and the ability to accurately monitor it in clinical practice.

描述 青光眼是一组导致视网膜神经节细胞(RGC)病理性丧失且不可逆转的疾病 视力丧失。虽然青光眼是一种具有特征性视神经头(ONH)改变的视神经病变，但风险 疾病的发生不是基于ONH结构，而是包括眼压(IOP)、中央动脉 角膜厚度、年龄、种族和家族史。在早期疾病中，视神经明显变细。 RGC丢失之前的头部(ONH)边缘组织。我们推测ONH神经视网膜的早期变薄 边缘组织(NRR)与胶质细胞和细胞外基质的变化有关，但与轴突含量无关，我们将 应用免疫组织化学和3D连续块面扫描电子显微镜研究非小细胞肺癌 人灵长类实验性青光眼模型。我们还假设ONH NRR对瞬变的响应 眼压的变化反映了NRR的组织成分，并预测了RGC丢失率(SA1)。 临床上，眼部的RGC含量通过光学相干断层扫描的非侵入性成像进行评估 (OCT)，用于结构，以及视觉阈值，用于功能。OCT结构性措施的可变性较低， 彻底改变了青光眼的评估方式。然而，研资局与OCT措施的对应关系尚不清楚， 而且不能从活体测量中估计。事实上，所有OCT派生的研资局措施的线性关系 是不正确的。SA2的OCT测量与视神经乳头周围神经纤维的关系 在神经病的所有阶段，神经层和神经节细胞内丛厚度将与RGC含量相关 严格的组织学方法。这一目标的目的是开发方法来估计眼睛中RGC的含量。为 这种疾病会导致不可逆转的视力丧失，重要的是也要准确地评估视觉功能。 原则上，根据OCT测量估计的RGC含量之间也应具有良好的一致性 这一点来自视觉阈值。由于结构性措施是客观的，变化较小，因此它将是理想的 使用结构性措施准确预测视力。然而，两者之间存在着显著的差异 结构性和功能性措施。这种分离的一些原因是视觉功能测试不能 使用适当的空间采样和刺激大小。在这些实验中，我们将研究它们之间的关系 使用更高的空间密度和不同的刺激大小(SA3)，RGC内容和视觉阈值之间的差异。我们的 目的是建立基于非侵入性结构成像的稳健的视觉功能预测方法。总的来说， 这些研究旨在提高我们对疾病病理生理学的理解和准确诊断疾病的能力 在临床实践中进行监测。