In vivo Ultrastructure of Chorioretinal Disease

脉络膜视网膜疾病的体内超微结构

基本信息

批准号：
10684031
负责人：
Yuhua Liang Zhang
金额：
$ 35.15万
依托单位：
DOHENY EYE INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-01-01 至 2024-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10684031
关键词：
Acceleration Age Age related macular degeneration Angiography Anterior Atrophic Basal lamina Blindness Blood Vessels Blood capillaries Blood flow Blood-Retinal Barrier Bruch&apos s basal membrane structure Characteristics Choroid Clinical Dedications Deposition Detection Development Disease Drusen Etiology Event Evolution Exudative age-related macular degeneration Eye Fluorescence Functional disorder Funding Gender Goals Health Health Status Image Imaging Techniques Impairment Individual Knowledge Lead Lesion Letters Measurement Measures Metabolic Methods Microcirculation Monitor Multimodal Imaging Natural History Ophthalmoscopes Ophthalmoscopy Optical Coherence Tomography Paper Pathway interactions Patients Peer Review Perfusion Photoreceptors Physiological Procedures Process Proliferating Race Research Resolution Retina Risk Assessment Side Specific qualifier value Speed Structure Structure of retinal pigment epithelium Surface System Testing adaptive optics cell motility cohort density early detection biomarkers extracellular fluorescence lifetime imaging hemodynamics high resolution imaging imaging biomarker improved in vivo macula migration monolayer neovascular neovascularization neurosensory novel retinal imaging success

项目摘要

Project Summary This renewal will address crucial knowledge gaps in the pathway that subretinal drusenoid deposits (SDD) lead to Type 3 macular neovascularization (T3MNV, also known as retinal angiomatous proliferation) in age-related macular degeneration (AMD). SDD are extracellular lesions present between photoreceptors and their supportive retinal pigment epithelium (RPE) cells. Thus they’re on the opposite side of the physiologic blood-retina-barrier to classical drusen, which are AMD’s hallmark lesions. Drusen accumulate on the inner surface of Bruch’s membrane posterior to the RPE. T3MNV is an important by less recognized form of neovascular AMD that has an intraretinal origin and can result in severe vision loss. SDD have a strikingly high occurrence in eyes with T3MNV. The distribution of T3MNV has a large overlap with that of SDD. T3MNV’s etiology is recently appreciated by advanced retinal imaging including optical coherence tomography (OCT) structure and angiography (OCTA). It’s been suggested that T3MNV originates from the deep capillary plexus (DCP) of the retina after precursory RPE cells migrate anteriorly. How SDD lead to T3MNV, and how retinal capillaries interact with precursor migratory RPE cells to initiate T3MNV is not completely understood. Nor is why and when RPE cells begin migration. We hypothesize that reduced or impaired metabolic supply due to dysfunction of the choriocapillaris or accumulation of extracellular lesions on both sides of the RPE are inciting events that promote RPE cells to leave their monolayer and migrate to the DCP, thereby eliciting neovascularization in the retina; this process can be significantly exacerbated by SDD. We thus propose to evaluate the health status of the retinal capillary system through in vivo characterization of the retinal capillary hemodynamics in relation to the developmental stage of SDD and drusen, the health of the RPE, and the structure of the choriocapillaris and the choroid, in patients with AMD. We’ve developed an adaptive optics (AO) enhanced high speed near confocal ophthalmoscope (AONCO), which can image the retina with cellular resolution and measure the high-order hemodynamics in retinal capillaries. We've developed novel method to estimate the choriocapillaris structure using OCTA. We obtained fluorescence lifetime imaging ophthalmoscopy (FLIO), which can assess RPE health. Our objectives are two-fold: understanding the pathway by which SDD lead to T3MNV and developing AO imaging based biomarkers for early detection of T3MNV. We predict: 1. High-order hemodynamic characteristics that measure the acceleration (and its change) of the blood flow within retinal capillaries may provide sensitive detection of abnormalities of the retinal microcirculation induced by early neovascular events that lead to T3MNV. 2. FLIO may provide an objective quantification of RPE health that correlates with the stages of SDD and drusen, and the health of the choriocapillaris. Success of this research will provide improved markers and endpoint for monitoring and treating T3MNV by objective measurements of RPE health and retinal vascular health, thereby, represents a significant stride toward our long-term goal that dedicates to improve the basis of assessing risk for AMD progression and clinical endpoints for evaluating treatments.

项目摘要这种更新将解决视网膜下drzenoid矿床（SDD）导致的关键知识差距与年龄相关的黄斑中的3型黄斑新生血管形成（T3MNV，也称为视网膜血管增生）变性（AMD）。 SDD是光感受器及其受支持的残留物之间存在的细胞外病变色素上皮（RPE）细胞。他们在物理血液蝙蝠的另一侧与古典 Drusen，是AMD的标志性病变。 drusen积聚在布鲁克膜后部的内表面到RPE。 T3MNV是一种重要的新血管AMD形式的重要形式，该形式具有视野内，并且可能导致严重的视力丧失。 T3MNV的眼睛中SDD的出现较高。分布 T3MNV与SDD的重叠很大。高级视网膜成像最近赞赏T3MNV的病因包括光学相干断层扫描（OCT）结构和血管造影（OCTA）。有人建议T3MNV 起源于预耐RPE细胞在前方迁移后视网膜的深毛细血管（DCP）。 SDD如何导致T3MNV，以及视网膜毛细血管如何与前体迁移RPE细胞相互作用以启动T3MNV不是完全理解。 RPE细胞开始迁移的原因也不是原因。我们假设减少或受损由于脉络膜毛细血管的功能障碍或在两侧的细胞外病变的积累引起的代谢供应 RPE正在煽动促进RPE细胞离开单层并迁移到DCP的事件，从而在视网膜中引起新血管化； SDD可能会大大加剧此过程。因此，我们建议通过视网膜毛细管的体内表征评估视网膜毛细管系统的健康状况与SDD和DRUSEN的发育阶段有关的血液动力学，RPE的健康以及结构 AMD患者的脉络膜毛细血管和脉络膜。我们已经开发了自适应光学器件（AO）共聚焦眼镜镜（Aonco）附近的高速速度，可以用细胞分辨率对视网膜进行成像测量视网膜毛细血管中的高阶血液动力学。我们已经开发了新颖的方法来估计脉络膜毛细血管结构使用八颗。我们获得了荧光寿命成像眼镜检查（FLIO），这是可以评估RPE健康。我们的目标是两个方面：了解SDD导致T3MNV和开发基于AO成像的生物标志物，用于早期检测T3MNV。我们预测：1。高阶血液动力学测量视网膜毛细血管内血流加速度（及其变化）的特征可能会提供早期的新生血管事件引起的视网膜微循环异常的敏感检测，导致 T3MNV。 2。FLIO可以提供客观数量的RPE健康，与SDD的阶段相关德鲁森（Drusen）和绒毛膜毛细血管的健康。这项研究的成功将提供改进的标记和终点通过客观测量RPE健康和残留血管健康，以监测和治疗T3MNV 代表着我们的长期目标的重大迈进，致力于改善评估风险的基础用于评估治疗的AMD进展和临床终点。