MRI BIOMARKERS OF ANGIOGENESIS AND CELL INJURY IN RETINOPATHY OF PREMATURITY

早产儿视网膜病变中血管生成和细胞损伤的 MRI 生物标志物

基本信息

批准号：
7450075
负责人：
Junjie Chen
金额：
$ 21.76万
依托单位：
WASHINGTON UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2008
资助国家：
美国
起止时间：
2008-03-01 至 2010-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7450075
关键词：
Acetic Acid Acetic Acids Adult Adverse effects Area Binding Biological Markers Blindness Cell Hypoxia Cells Child Cornea Diagnostic Procedure Diffusion Diffusion Magnetic Resonance Imaging Disease Marker Disease Progression Early Diagnosis Fluorocarbons Gadolinium Hyperglycemia Hypoxia Imaging Techniques Integrins Invasive Lead Localized Magnetic Resonance Magnetic Resonance Imaging Malignant - descriptor Measures Medical Medical Imaging Methods Modeling Molecular Neonatal Operative Surgical Procedures Oryctolagus cuniculus Oxygen Oxygen Consumption Pathologic Neovascularization Patients Pentas Peripheral Pharmaceutical Preparations Photoreceptors Premature Infant Preventive Public Health Rattus Research Resolution Retina Retinal Retinal Detachment Retinal Diseases Retinal Neovascularization Retinopathy of Prematurity Rodent Specific qualifier value Surface Techniques Testing Tumor-Associated Vasculature Vision Visual system structure Weight angiogenesis antiangiogenesis therapy base cell injury cost diabetic diethylenetriamine experience indexing injured interest nanoparticle novel novel diagnostics photoreceptor degeneration prevent proliferative diabetic retinopathy retinal angiogenesis retinal ischemia tool

项目摘要

DESCRIPTION (provided by applicant): Proliferative retinopathy is a leading cause of blindness in adults and children. It is manifested as hypoxia induced malignant angiogenesis at retinal surface that will deteriorate vision and lead to retinal detachment to cause permanent vision loss. Medical therapy for proliferative retinopathy is non-effective. Surgical medical treatment to ablate peripheral retina is the method to prevent the disease progression at the cost of losing peripheral vision. This treatment has prominent side effects on the visual system and may not stop the disease progression in some patients. Current interests on developing more effective therapy for proliferative retinopathy are: to develop anti-angiogenesis drug that specifically inhibit retinal neovascularization; to explore predictive markers of the diseases for preventive therapy. We have developed high resolution magnetic resonance imaging (MRI) technique that specifies multiple retinal layers with layer specific T1, T2, and apparent diffusion coefficient (ADC) in rodents. Our preliminary studies have demonstrated that MRI is sensitive to cell injury after retinal ischemia or photoreceptor degeneration. We have also shown that 1v23-integrin targeted nanoparticles specifically bind to corneal neovasculature and provide localized MRI contrast in rabbits. Based on our preliminary result, we hypothesize that hypoxia induced retinal angiogenesis could be specifically delineated with molecular MRI using 1v23-integrin targeted nanoparticles. Hypoxia will also cause retinal cell injury that will result in changes in ADC before retinal angiogenesis. To test our hypothesis, a rat model of hypoxia induced retinal neovascularization is selected. We predict that 1v23-integrin targeted nanoparticles will specifically bind to retinal neovasculature for molecular MRI of retinal angiogenesis. We also expect changes in ADC in hypoxia injured retinal cells can be detected early with diffusion weighted magnetic resonance imaging. The proposed study, if successful, will provide novel MRI biomarkers for early diagnosis of retinal neovascularization that feature cell hypoxia and angiogenesis. PUBLIC HEALTH RELEVANCE: Retinal angiogenesis is the leading cause of blindness in premature infants and diabetic adults. The proposed research aims to develop techniques for early diagnosis of retinal angiogenesis using nanoparticles and non-invasive medical imaging method.

描述（由申请人提供）：增生性视网膜病是成人和儿童失明的主要原因。它表现为缺氧在视网膜表面引起的恶性血管生成，这将使视力恶化并导致视网膜脱离导致永久视力丧失。增殖性视网膜病的药物治疗无效。为消除外周视网膜的手术医学治疗是防止疾病进展的方法，以失去外围视力为代价。这种治疗对视觉系统产生了显着的副作用，并且可能不会阻止某些患者的疾病进展。目前对开发更有效治疗的增殖性视网膜病的兴趣是：开发特定抑制视网膜新生血管形成的抗血管生成药物；探索预防疗法疾病的预测标志物。我们已经开发了高分辨率磁共振成像（MRI）技术，该技术指定了啮齿动物中具有层特异性T1，T2和明显扩散系数（ADC）的多个视网膜层。我们的初步研究表明，MRI对视网膜缺血或感光体变性后的细胞损伤敏感。我们还表明，具有1V23-整合素的靶向纳米颗粒特异性结合了角膜新脉管系统，并在兔子中提供了局部的MRI对比。基于我们的初步结果，我们假设使用1V23-整合素靶向纳米颗粒可以通过分子MRI特异性地划定缺氧引起的视网膜血管生成。缺氧还会引起视网膜细胞损伤，这会导致视网膜血管生成之前的ADC变化。为了检验我们的假设，选择了缺氧诱导的视网膜新血管形成的大鼠模型。我们预测，1V23-积聚蛋白靶向的纳米颗粒将特异性结合视网膜新脉管系统，以进行视网膜血管生成的分子MRI。我们还期望通过扩散加权磁共振成像早期检测到缺氧损伤细胞中ADC的变化。拟议的研究（如果成功）将提供新颖的MRI生物标志物，以早期诊断为视网膜新血管形成，具有细胞缺氧和血管生成。公共卫生相关性：视网膜血管生成是早产儿和糖尿病成年人失明的主要原因。拟议的研究旨在开发使用纳米颗粒和非侵入性医学成像方法早期诊断视网膜血管生成的技术。