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）的病理性损失和不可逆的视网膜病变的疾病。 视力丧失虽然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 发展中疾病的发病率不是基于ONH结构，而是包括眼内压（IOP）、中枢神经系统疾病（CNS）、 角膜厚度、年龄、种族和家族史。在疾病早期，视神经明显变薄 头（ONH）边缘组织之前RGC损失。我们假设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 使用免疫组织化学和3D连续块面扫描电子显微镜研究非 人灵长类实验性青光眼模型。我们还假设ONH NRR对短暂的 IOP的变化是NRR组织组成的反映，并且是RGC损失率的预测（SA1）。 临床上，使用光学相干断层扫描的非侵入性成像评估眼睛的RGC含量 (OCT)结构的阈值，功能的阈值。OCT结构测量具有低可变性， 彻底改变了青光眼的评估方法。然而，RGC与OCT测量的对应关系尚不清楚， 并且不能从体内测量中估计。事实上，所有OCT导出的RGC测量的线性关系 是不正确的。在SA2中，视乳头周围视网膜神经纤维的OCT衍生测量之间的关系 层和神经节细胞内丛状厚度将与RGC含量在所有阶段的神经病变，使用 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 这种疾病会导致不可逆的视力丧失，因此准确评估视功能也很重要。 原则上，OCT测量的RGC含量估计值之间也应该有很好的对应关系 and that from visual视觉threshold阈值.由于结构性措施是客观的，可变性较小， 使用结构测量准确预测视力。然而，两者之间存在显著差异。 结构和功能措施。这种分离的部分原因是视觉功能测试不 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 使用更高的空间密度和不同的刺激大小（SA3）的RGC内容和视觉阈值之间。我们 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。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， 在临床实践中进行监测。