Molecular and Clinical Pharmacology of Retinopathy of Prematurity

早产儿视网膜病变的分子和临床药理学

基本信息

批准号：
8338895
负责人：
JACOB V ARANDA
金额：
$ 77.15万
依托单位：
SUNY DOWNSTATE MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2016-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8338895
关键词：
Area Astrocytes Awareness Behavior Blindness Caffeine Cell Culture Techniques Cells Child Childhood Clinical Clinical Pharmacology Communities Darkness Data Development Drops Drug Transport Drug effect disorder Drug usage Event Eye Eyedrops General Population Health Hyperoxia Hypoxia Ibuprofen Interdisciplinary Study Intervention Ketorolac Life Modeling Molecular Neonatal New York Newborn Infant Non-Steroidal Anti-Inflammatory Agents Oxidative Stress Oxygen Performance Perinatal Pharmaceutical Preparations Pharmacodynamics Pharmacogenomics Pharmacologic Substance Pharmacology Phase Premature Infant Prevention Preventive Intervention Protocols documentation Randomized Rattus Research Research Activity Research Personnel Retina Retinal Retinal Diseases Retinopathy of Prematurity Safety Scientist Signal Transduction Staging Testing Time Training Training Programs Translational Research Vascular Endothelial Growth Factors angiogenesis career development disability multidisciplinary novel open label pediatric pharmacology prevent programs safety testing

项目摘要

DESCRIPTION (provided by applicant): Retinopathy of prematurity (ROP) occurs in 50 to 80% of preterm babies born weighing less than 1250 grams. The NYPD-PRC (New York Pediatric Developmental Pharmacology Research Consortium) was formed as a unique multidisciplinary research team of neonatal pharmacologist, retina investigators, neonatologists and pharmaceutical scientists to define the molecular events leading to ROP and to develop effective and safe pharmacologic strategies to prevent it. The overarching hypothesis is that repeated hyperoxic/hypoxic episodes promoting aberrant ocular VEGF signaling, dysregulated angiogenesis and vasoproliferation can be modulated or prevented by synergistic interventions of caffeine and systemic ibuprofen or ocular NSAID local drops. Using novel intervention strategies and unique approaches, three distinct but highly inter-related study proposals will test various hypotheses and specific aims in newborn rats, retinal endothelial tip cell cultures and in preterm newborn infants born <28 weeks or weighing <1250 grams. Protocol 1 will determine the efficacy and safety of ocular ibuprofen or ketorolac with systemic caffeine as well as the critical timing of intervention for the prevention of oxygen induced retinopathy in newborn rat model of OIR. Protocol II will examine the behavior of retinal endothelial tip cells and their dynamic relationship with astrocytes in the setting of oxidative stress (hyperoxia/hypoxia cycling); and to determine whether ibuprofen co-administered with caffeine will preserve tip cell quiescence. Once studies on additional safety, efficacy and critical timing of intervention (vasoobliterative or vaso-proliferative phase) are completed, Protocol III will be implemented in preterm newborns weighing <1250 grams, to test the safety, efficacy, pharmacodynamics and pharmacogenomics of systemic caffeine with or without IV ibuprofen or with or without local NSAID eye drops (ketorolac) in a multicenter, randomized, open label study to prevent ROP (all stages). Unique pharmacometric analyses of all 3 protocols provide novel data on ocular drug transport and action during development. The NYPD-PRC will surely elevate the level of scientific inquiry on molecular and clinical pharmacology of ROP to hasten its prevention and avert life-long blindness.

描述（由申请人提供）：早产（ROP）的视网膜病变发生在50％至80％的早产婴儿中，体重小于1250克。 NYPD-PRC（纽约儿科发展药理学研究联盟）被成立为新生儿药理，视网膜研究者，新生儿学家和制药科学家的独特多学科研究团队，以定义导致ROP并制定有效和安全的药理学策略来预防其的分子事件。总体假设是，可以通过咖啡因和全身性ibuprofen或Ocular nsaid Nsaid Nosaid局部滴剂来调节或预防重复的高氧/低氧发作，促进异常的眼VEGF信号，血管生成失调和血管增生。使用新颖的干预策略和独特的方法，将测试三个不同但高度相关的研究建议新生大鼠，视网膜内皮尖端细胞培养物以及早产的新生婴儿出生<28周或称重<1250 克。协议1将确定具有全身性的眼部布洛芬或Ketorolac的功效和安全性咖啡因以及预防氧诱导视网膜病变的干预措施的关键时机 OIR的新生大鼠模型。协议II将检查视网膜内皮尖端细胞及其其行为在氧化应激（高氧/缺氧循环）中与星形胶质细胞的动态关系；并确定布洛芬是否与咖啡因共同采用会保持尖端细胞的静止。 Once studies on additional safety, efficacy and critical timing of intervention (vasoobliterative or vaso-proliferative phase) are completed, Protocol III will be implemented in preterm newborns weighing <1250 grams, to test the safety, efficacy, pharmacodynamics and pharmacogenomics of systemic caffeine with or without IV ibuprofen or with or without local NSAID eye drops (ketorolac) in a多中心，随机，开放标签研究以防止ROP（所有阶段）。所有3个方案的独特药物测量分析提供了有关开发过程中眼药运输和作用的新数据。 NYPD-PRC肯定会提高ROP分子和临床药理学的科学研究水平，以加快其预防并避免终身失明。