In vivo ultrastructure of chorioretinal disease

脉络膜视网膜疾病的体内超微结构

• 批准号: 9198233
• 负责人: Yuhua Liang Zhang
• 金额: $ 36.75万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9198233
• 关键词: 3-Dimensional; Affect; Age related macular degeneration; American; Anterior; Area; Biogenesis; Biological Markers; Biometry; Blindness; Bruch' s basal membrane structure; Cells; Choroid; Choroidal Neovascularization; Clinical; Cone; Deposition; Development; Disease; Drusen; Elderly; Functional disorder; Goals; Health; Histology; Homeostasis; Human; Image; Imaging Device; Imaging technology; Impairment; Individual; Interruption; Lasers; Lesion; Lesion by Stage; Lipids; Location; Measures; Mediating; Modeling; Natural History; Nonexudative age-related macular degeneration; Nuclear; Ophthalmoscopy; Optical Coherence Tomography; Optics; Patients; Photoreceptors; Process; Psychophysics; Resolution; Retina; Retinal; Retinal Degeneration; Risk; Risk Factors; Role; Route; Scanning; Structure; Structure of retinal pigment epithelium; Surface; System; Testing; Thick; Vertebrate Photoreceptors; Vision; Visit; adaptive optics; base; clinical diagnostics; clinical imaging; density; drug development; extracellular; geographic atrophy; high resolution imaging; imaging modality; improved; in vivo; instrument; multimodality; next generation; novel; novel therapeutics; optical imaging; photoreceptor degeneration; public health relevance; retinal rods; treatment strategy

 DESCRIPTION (provided by applicant): Age-related macular degeneration (AMD) is a leading cause of vision loss in more than 10 million older Americans. For decades, AMD has been characterized by accumulation of extracellular lesions called drusen on the inner surface of Bruch's membrane (BrM), posterior to the retinal pigment epithelium (RPE), in a compartment called the sub-RPE space. Drusen are now recognized as the best known half of a larger system postulated for outer retinal lipid homeostasis that includes highly prevalent extracellular lesions in a compartment called the subretinal space, between the photoreceptors and RPE. Subretinal drusenoid deposits (SDD), which accumulate anterior to the RPE, are thought to clinically manifest as reticular pseudodrusen (RPD). These biomicroscopic signs visible in multiple imaging modalities are highly associated with progression to choroidal neovascularization (CNV) and geographic atrophy (GA), AMD's two late stages. The disparate location of RPD compared to that of classical drusen implies different impact on overlaying photoreceptor cells, different processes leading to late stage AMD, and different biogenesis mechanisms. The effect of RPD on overlying photoreceptors and why RPD are significant risk factors for vision loss remains mysterious. We hypothesize that RPD/SDD, like drusen, are biomicroscopic signs of chorioretinal degeneration that impact the structure and function of photoreceptors at both formative and regressing stages. We predict that RPD/SDD will have more impact on photoreceptors than drusen, because they are in the sub-retinal space and therefore in direct contact with photoreceptors. We further predict that rods will more be affected than cones in both lesions, because the rods are more vulnerable to interruption of their supply route from the choroid than are cones. Thus, we propose to characterize the ultrastructure and natural history of RPD, in relation to the structure and function of overlaying photoreceptors and RPE/choroid health in patients with non- neovascular AMD. Our objectives are two-fold: better understanding of RPD's role in the pathophysiology of AMD, and developing adaptive optics (AO) imaging based biomarkers and biometrics for sensitive and quantitative assessment of photoreceptor degeneration in AMD. We have developed a novel AO imaging instrument that integrates scanning laser ophthalmoscopy and optical coherence tomography (AO-SLO-OCT). This instrument can image the retina with 3-D spatial resolution of 2.5 µm X 2.5 µm X 5 µm thereby allowing for in-vivo ultrastructure assessment of RPD and individual photoreceptors in both en face and cross-sectional planes. We will accomplish our goals by use of AO high resolution imaging and standard multimodal clinical imaging.

 描述（由申请人提供）：年龄相关性黄斑变性 (AMD) 是超过 1000 万美国老年人视力丧失的主要原因。几十年来，AMD 的特点是在视网膜色素上皮 (RPE) 后面的布鲁赫膜 (BrM) 内表面，称为 RPE 下空间的室中，称为玻璃膜疣的细胞外病变积聚。玻璃膜疣现在被认为是假定外层视网膜脂质稳态的较大系统中最著名的一半，该系统包括光感受器和视网膜色素上皮之间称为视网膜下间隙的室中高度普遍的细胞外病变。视网膜下玻璃膜疣沉积物 (SDD) 聚集在 RPE 前方，临床上被认为表现为网状假性玻璃膜疣 (RPD)。这些在多种成像方式中可见的生物显微镜迹象与脉络膜新生血管 (CNV) 和地图样萎缩 (GA)（AMD 的两个晚期阶段）的进展高度相关。与经典玻璃膜疣相比，RPD 的不同位置意味着对覆盖感光细胞的不同影响、导致晚期 AMD 的不同过程以及不同的生物发生机制。 RPD 对上层光感受器的影响以及为什么 RPD 是视力丧失的重要危险因素仍然是个谜。我们假设 RPD/SDD 与玻璃膜疣一样，是脉络膜视网膜变性的生物显微镜迹象，会影响光感受器形成和退化阶段的结构和功能。我们预测 RPD/SDD 对感光器的影响比玻璃膜疣更大，因为它们位于视网膜下空间，因此与感光器直接接触。我们进一步预测杆将受到更大的影响 在两个病变中，视杆细胞比视锥细胞更容易受到影响，因为视杆细胞比视锥细胞更容易受到来自脉络膜的供应路线的干扰。因此，我们建议描述非新生血管性AMD患者的RPD超微结构和自然史，以及与覆盖光感受器的结构和功能以及RPE/脉络膜健康相关的特征。我们的目标有两个：更好地了解 RPD 在 AMD 病理生理学中的作用，并开发基于自适应光学 (AO) 成像的生物标志物和生物识别技术，用于对 AMD 光感受器变性进行灵敏和定量评估。我们开发了一种新型的AO成像仪器，集成了扫描激光检眼镜和光学相干断层扫描（AO-SLO-OCT）。该仪器可以以 2.5 µm X 2.5 µm X 5 µm 的 3D 空间分辨率对视网膜进行成像，从而可以对正面和横截面的 RPD 和单个感光器进行体内超微结构评估。我们将通过使用 AO 高分辨率成像和标准多模态临床成像来实现我们的目标。