Relating Structure to Function in Optic Neuropathies

视神经病变的结构与功能的关系

• 批准号: 10547776
• 负责人: Nimesh Bhikhu Patel
• 金额: $ 38.25万
• 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 2024-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10547776
• 关键词: 3-Dimensional; Acute; Affect; Age; Agreement; Anatomy; Appearance; Area; Autopsy; Axon; Basic Science; Blindness; Cell Density; Characteristics; Clinical; Cornea; Data; Diagnosis; Disease; Disease Management; Electroretinography; Epidemiology; Extracellular Matrix; Eye; Face; Family; Functional disorder; Glaucoma; Goals; Healthcare; Histologic; Immunohistochemistry; Individual; Individual Differences; Inner Plexiform Layer; Investigation; Knowledge; 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; Predisposition; Prevalence; Public Health; Race; Recording of previous events; Research; Retina; Retinal Ganglion Cells; Risk; Sampling; Scanning; Scanning Electron Microscopy; Stimulus; Structure; Technology; Testing; Thick; Thinness; Tissues; United States; Vision; blind; clinical practice; density; design; diagnostic technologies; disorder risk; experimental study; ganglion cell; histological studies; improved; in vivo; neural; non-invasive imaging; nonhuman primate; optic nerve disorder; predictive modeling; response; retinal damage; retinal nerve fiber layer; structural imaging; 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。尽管青光眼是一种具有特征性视神经乳头 (ONH) 变化的视神经病变，但风险 疾病的发生与否并非基于 ONH 结构，而是基于眼压 (IOP)、中枢神经系统等因素。 角膜厚度、年龄、种族和家族史。在疾病早期，视神经明显变薄 RGC 损失之前的头部 (ONH) 边缘组织。我们假设 ONH 神经视网膜的早期变薄 边缘组织（NRR）与神经胶质和细胞外基质的变化有关，但与轴突含量无关，我们将其 使用免疫组织化学和 3D 连续块面扫描电子显微镜研究非 人类灵长类实验性青光眼模型。我们还假设 ONH NRR 对瞬态的响应 IOP 的变化反映了 NRR 组织成分，并可预测 RGC 损失率 (SA1)。 临床上，使用光学相干断层扫描技术通过非侵入性成像来评估眼睛的 RGC 内容 （OCT）用于结构，视觉阈值用于功能。 OCT 结构测量具有低变异性，并且具有 彻底改变了青光眼的评估方式。然而，RGC 与 OCT 措施的对应关系尚不清楚， 并且不能通过体内测量来估计。事实上，所有 OCT 衍生的 RGC 测量值均呈线性关系 是不正确的。在 SA2 中，OCT 衍生的环乳头视网膜神经纤维测量值之间的关系 层和神经节细胞内丛状厚度将与神经病变各个阶段的 RGC 含量相关 严格的组织学方法。该目标的目标是开发估计眼睛中 RGC 含量的方法。为了 这种疾病会导致不可逆的视力丧失，因此准确评估视觉功能也很重要。 原则上，OCT 测量的 RGC 含量估计值之间也应该具有良好的对应性 以及来自视觉阈值的信息。由于结构性措施是客观的且变化较小，因此这是理想的 使用结构测量准确预测视力。但两者之间存在显着差异 结构和功能措施。造成这种脱节的部分原因是视功能测试不 使用适当的空间采样和刺激大小。在这些实验中，我们将研究这种关系 使用更高的空间密度和不同的刺激大小（SA3）在 RGC 内容和视觉阈值之间进行比较。我们的 目标是建立基于非侵入性结构成像的稳健方法来预测视觉功能。全面的， 这些研究旨在提高我们对疾病病理生理学的理解以及准确诊断的能力 在临床实践中对其进行监测。