High-resolution imaging of the normal and diseased retina

正常和患病视网膜的高分辨率成像

• 批准号: 8312497
• 负责人: Jason Porter
• 金额: $ 36.8万
• 依托单位: UNIVERSITY OF HOUSTON
• 依托单位国家: 美国
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8312497
• 关键词: Age; Anterior; Area; Autopsy; Axon; Blindness; Blood Vessels; Caliber; Cell Death; Cessation of life; Clinical; Contralateral; Data; Development; Diagnosis; Diagnostic Imaging; Disease; Disease Progression; Early Diagnosis; Electroretinography; Etiology; Experimental Models; Eye; Fundus photography; Future; Glaucoma; Goals; Health; Height; Human; Image; Imaging Techniques; Knowledge; Lasers; Lateral; Lead; Life; Light; Macaca; Macaca mulatta; Measurement; Measures; Mechanics; Methods; Mission; Monkeys; Morphology; National Institute of Biomedical Imaging and Bioengineering; Nerve Degeneration; Nerve Fibers; Neural Canal; Neurons; Ophthalmoscopes; Optic Disk; Optic Nerve; Optical Coherence Tomography; Optics; Pathology; Patients; Pattern; Perimetry; Primary Open Angle Glaucoma; Procedures; Property; Relative (related person); Research; Resolution; Retina; Retinal Diseases; Retinal Ganglion Cells; Risk Factors; Role; Scanning; Severity of illness; Shapes; Site; Staging; Surface; Techniques; Testing; Thick; Time; Tissue Model; Vision; Visual Fields; Work; adaptive optics; age related; base; bioimaging; clinically significant; density; imaging modality; improved; in vivo; innovation; insight; instrument; nonhuman primate; normal aging; novel; optical imaging; pressure; prevent; research study; response; retinal nerve fiber layer; retinal neuron; tool

Glaucoma is the second leading cause of blindness worldwide and results in the degeneration of retinal ganglion cell axons and retinal ganglion cell (RGC) death. Strong evidence supports the idea that RGC axons are initially damaged due to structural alterations in the lamina cribrosa within the optic nerve head (ONH). However, the vast majority of supporting studies are based on data from excised eyes. A lack of high- resolution in vivo imaging data of the normal and glaucomatous lamina cribrosa has prevented thorough understanding of the impact of changes in laminar geometry on disease progression in the living eye. This proposed work will test the hypothesis that structural alterations in laminar pores underlie subsequent axonal damage and vision loss in the normal aged eye and eyes with glaucoma. The hypothesis will be examined by pursuing three specific aims. The first aim will measure in vivo changes in laminar pore geometry over the time course of experimental glaucoma in macaque monkeys with a confocal adaptive optics scanning laser ophthalmoscope (AOSLO). These data will be combined with changes in visual function (standard automated perimetry and electroretinography) and retinal nerve fiber layer (RNFL) thickness (using optical coherence tomography) at corresponding time-points to test the hypothesis that laminar pore changes precede axonal and vision loss in experimental glaucoma. The second aim will determine age-related differences in laminar pore geometry in normal living human eyes using the AOSLO and test the hypothesis that laminar pore size increases with age and is associated with small increases in cupping (measured via fundus photography) and decreased RNFL thickness and visual function. The last aim applies the same methods to measure laminar pore geometry in patients with primary open-angle glaucoma. It will test the hypothesis that larger pore sizes and increased cupping occur in eyes with increasing disease severity and are correlated with decreases in RNFL thickness and visual function. This research plan is based on defining procedures and relationships with experimental glaucoma and extending them to human patients to test their clinical significance. It is aligned with the missions of the NEI and NIBIB in that it investigates a potential mechanism underlying a blinding retinal disease and seeks to improve the diagnosis and assessment of glaucoma in human patients via a new application of a biomedical imaging technique (i.e., AOSLO imaging). The approach is innovative because it uses confocal AOSLO imaging to increase the lateral resolution and contrast of laminar images relative to current clinical instruments, thereby allowing laminar pore geometry to be reliably measured in living normal and glaucomatous eyes. The proposed research is significant because it will lead to more sensitive in vivo imaging techniques to examine structural changes and better clarify the etiology of glaucoma. Ultimately, such knowledge will enhance our understanding of the lamina's role in the development and progression of this disease and may provide an earlier marker of structural damage (i.e., laminar pore alteration) in glaucoma.

青光眼是全球失明的第二大主要原因，并导致视网膜退化 神经节细胞轴突和视网膜神经节细胞（RGC）死亡。有力的证据支持RGC轴突的想法 最初由于视神经头（ONH）内的椎板纤维片的结构改变而受到损害。 但是，绝大多数支持研究基于切除的眼睛的数据。缺乏高 分辨率在正常和青光眼薄片的体内成像数据已阻止 了解层流几何形状对活眼疾病进展的影响的影响。这 拟议的工作将检验以下假设：层状孔的结构改变是随后的轴突 正常老年眼睛的损伤和视力丧失，具有青光眼的眼睛。该假设将通过 追求三个具体目标。第一个目标将在整个时间内测量层孔几何形状的体内变化 猕猴的实验青光眼疗程，具有共聚焦自适应光学扫描激光 眼镜镜（AOSLO）。这些数据将与视觉功能的变化结合（标准自动化 周长和电子图）和视网膜神经纤维层（RNFL）厚度（使用光学相干性 层析成像）在相应的时间点以测试层状孔变化的假设之前 和实验青光眼的视力丧失。第二个目标将确定与年龄相关的层次差异 使用AOSLO，正常活着的人眼的孔几何形状，并测试了层孔尺寸的假设 随着年龄的增长而增加，与拔罐的少量增加有关（通过眼底摄影测量）和 降低了RNFL厚度和视觉功能。最后的目标应用了相同的方法来测量层流 原发性开角青光眼患者的孔几何形状。它将测试较大孔径的假设 拔罐的增加发生在疾病严重程度增加，与下降相关 RNFL厚度和视觉功能。该研究计划基于定义程序和与 实验性青光眼并将其扩展到人类患者以测试其临床意义。它是对齐的 随着NEI和Nibib的任务，它研究了盲人的潜在机制 视网膜疾病，并试图通过新的 生物医学成像技术的应用（即AOSLO成像）。这种方法是创新的，因为它 使用共聚焦AOSLO成像来增加层流图像相对于层状图像的横向分辨率和对比度 当前的临床仪器，从而可以在正常生活中可靠地测量层状孔的几何形状 和青光眼的眼睛。拟议的研究很重要，因为它将导致体内更敏感 检查结构变化并更好地阐明青光眼的病因的成像技术。最终，这样的 知识将增强我们对薄片在发展和发展中的作用的理解 疾病并可能提供青光眼中结构损伤（即层状孔的改变）的早期标志。