MRI BIOMARKERS OF ANGIOGENESIS AND CELL INJURY IN RETINOPATHY OF PREMATURITY

描述（由申请人提供）：视网膜病变是成人和儿童失明的主要原因。它表现为缺氧诱导视网膜表面恶性血管生成，使视力下降，导致视网膜脱离，造成永久性视力丧失。增殖性视网膜病变的药物治疗无效。切除周边视网膜的手术治疗是以丧失周边视力为代价防止疾病进展的方法。这种治疗对视觉系统有明显的副作用，并且可能无法阻止某些患者的疾病进展。目前对增殖性视网膜病变的治疗主要集中在：开发特异性抑制视网膜新生血管的抗血管生成药物;寻找增殖性视网膜病变的预测标志物以进行预防性治疗。我们已经开发了高分辨率磁共振成像（MRI）技术，指定多个视网膜层与层特定的T1，T2，和表观扩散系数（ADC）在啮齿动物。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敏感。我们还表明，1v 23-整合素靶向纳米颗粒特异性结合角膜新生血管，并提供局部MRI对比在兔子。基于我们的初步结果，我们假设缺氧诱导的视网膜血管生成可以用分子MRI使用1v 23-整合素靶向纳米颗粒进行特异性描绘。缺氧也会导致视网膜细胞损伤，这将导致视网膜血管生成之前ADC的变化。 为了验证我们的假设，选择了缺氧诱导的视网膜新生血管的大鼠模型。我们预测1v 23-整合素靶向纳米颗粒将特异性结合视网膜新生血管，用于视网膜血管生成的分子MRI。我们还期望弥散加权磁共振成像可以早期检测缺氧损伤视网膜细胞ADC的变化。这项研究如果成功，将为视网膜新生血管的早期诊断提供新的MRI生物标志物，其特征是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人失明的主要原因。该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.