MRI BIOMARKERS OF ANGIOGENESIS AND CELL INJURY IN RETINOPATHY OF PREMATURITY

描述(申请人提供)：增殖性视网膜病变是成人和儿童失明的主要原因。主要表现为低氧诱导的视网膜表面恶性血管生成，导致视力下降，导致视网膜脱离，导致永久性视力丧失。增殖性视网膜病变的内科治疗无效。手术治疗周边视网膜是以丧失周边视力为代价来阻止疾病进展的方法。这种疗法对视觉系统有明显的副作用，在一些患者中可能无法阻止疾病的发展。目前开发更有效的治疗增殖性视网膜病变的方法的兴趣是：开发特异性抑制视网膜新生血管的抗血管生成药物；探索疾病的预测标记物以用于预防治疗。我们已经开发出高分辨率磁共振成像(MRI)技术，该技术可以在啮齿类动物中确定具有层特异性T1、T2和表观扩散系数(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细胞变性后的细胞损伤很敏感。我们还展示了1v23-整合素靶向纳米颗粒与角膜新生血管的特异性结合，并在兔身上提供了局部的MRI对比。根据我们的初步结果，我们假设可以使用1v23-整合素靶向纳米颗粒用分子磁共振来特异性地描绘缺氧诱导的视网膜血管生成。缺氧还会造成视网膜细胞损伤，导致视网膜血管生成前ADC的变化。为了验证我们的假设，我们选择了一个低氧诱导的视网膜新生血管的大鼠模型。我们预测，1v23-整合素靶向纳米颗粒将特异性结合到视网膜新生血管上，用于视网膜血管生成的分子磁共振。我们还期望通过扩散加权磁共振成像可以早期发现缺氧损伤的视网膜细胞中ADC的变化。这项拟议的研究如果成功，将为视网膜新生血管的早期诊断提供新的MRI生物标志物，这些新生血管以细胞缺氧和血管生成为特征。公共卫生相关性：视网膜血管生成是早产儿和糖尿病成人失明的主要原因。这项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。

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.