In vivo ultrastructure of chorioretinal disease

脉络膜视网膜疾病的体内超微结构

• 批准号: 8989101
• 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/8989101
• 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; Diagnostic; Disease; Drusen; Elderly; Exudative age-related macular degeneration; Functional disorder; Goals; Health; Histology; Homeostasis; Human; Image; Imaging Device; Imaging technology; Individual; Interruption; Lasers; Lesion; Lesion by Stage; Lipids; Location; Measures; Mediating; Modeling; Natural History; Nuclear; Ophthalmoscopy; Optical Coherence Tomography; Optics; Patients; Photoreceptors; Process; Resolution; Retina; Retinal; Retinal Degeneration; Risk; Risk Factors; Role; Route; Scanning; Staging; Structure; Structure of retinal pigment epithelium; Surface; System; Testing; Thick; Vertebrate Photoreceptors; Vision; Visit; adaptive optics; base; density; drug development; extracellular; geographic atrophy; imaging modality; improved; in vivo; instrument; next generation; novel; novel therapeutics; optical imaging; photoreceptor degeneration; 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) 是导致超过 1000 万美国老年人视力丧失的主要原因。几十年来，AMD 的特点是在布鲁赫内表面积聚称为玻璃膜疣的细胞外病变。位于视网膜色素上皮 (RPE) 后面的视网膜色素上皮 (RPE) 下的膜 (BrM)，位于称为玻璃膜疣下空间的隔室中，现在被认为是假设的较大系统中最著名的一半。视网膜外层脂质稳态，包括光感受器和 RPE 之间称为视网膜下间隙的室中高度普遍的细胞外病变，其积聚在 RPE 之前，被认为临床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）的进展高度相关， AMD 的两个晚期阶段与经典玻璃疣相比，RPD 的不同位置意味着对覆盖的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 对覆盖的感光细胞的影响以及为什么 RPD 具有重大风险。我们勇敢地说，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，会影响光感受器的结构和功能。我们预测 RPD/SDD 对光感受器的影响比玻璃膜疣更大，因为它们位于视网膜下空间，因此与光感受器直接接触，我们进一步预测视杆细胞将受到更大的影响。 在这两种病变中，视杆细胞比视锥细胞更容易受到脉络膜供应路径的干扰，因此，我们建议根据覆盖的光感受器和视锥细胞的结构和功能来描述 RPD 的超微结构和自然史。非新生血管性 AMD 患者的 RPE/脉络膜健康我们的目标有两个：更好地了解 RPD 在 AMD 病理生理学中的作用，以及开发基于自适应光学 (AO) 成像的生物标志物和药物。我们开发了一种新型 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 3D 空间分辨率对视网膜进行成像。 2.5 µm X 2.5 µm X 5 µm，从而可以对面部和面部的 RPD 和单个光感受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。