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首页> 外文期刊>Frontiers in Neuropharmacology >Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies
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Exploration of Oxygen-Induced Retinopathy Model to Discover New Therapeutic Drug Targets in Retinopathies

机译：氧诱导的视网膜病变模型发现患有新疗效的治疗药物靶向疗效

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Oxygen-induced retinopathy (OIR) is a pure hypoxia-driven angiogenesis model and the most widely used model for ischemic retinopathies, such as retinopathy of prematurity (ROP), proliferative diabetic retinopathy (PDR), and retinal vein occlusion (RVO). OIR model has been used to test new potential anti-angiogenic factors for human diseases. We have recently performed the most comprehensive characterization of OIR by a relatively novel mass spectrometry (MS) technique, sequential window acquisition of all theoretical fragment ion mass spectra (SWATH-MS) proteomics and used genetically modified mice strains to identify novel molecular drug targets in angiogenic retinal diseases. We have confirmed the relevance of the identified molecular targets to human diseases by determining their expression pattern in neovascular membranes obtained from PDR and RVO patients. Based on our results, crystallins were the most prominent proteins induced by early hypoxic environment during the OIR, while actomyosin complex and Filamin A-R-Ras axis, that regulates vascular permeability of the angiogenic blood vessels, stood out at the peak of angiogenesis. Our results have revealed potential new therapeutic targets to address hypoxia-induced pathological angiogenesis and the associated vascular permeability in number of retinal diseases.
机译：氧气诱导的视网膜病变（OIR）是纯缺氧驱动的血管生成模型和最广泛使用的缺血性视网膜病模型，例如早产儿（ROP）的视网膜病变，增殖性糖尿病视网膜病变（PDR）和视网膜静脉闭塞（RVO）。 OIR模型已被用于测试人类疾病的新潜在的抗血管生成因子。我们最近通过相对新颖的质谱（MS）技术，顺序窗口获取所有理论片段离子质谱（SWATH-MS）蛋白质组学的序列窗口和使用遗传修饰的小鼠菌株来进行最全面的OIR表征，以鉴定新的分子药物靶标血管生成视网膜疾病。通过确定从PDR和RVO患者获得的新生血管膜中的表达模式，我们已经证实了所识别的分子靶标对人类疾病的相关性。基于我们的结果，晶体素是在奥尔血管发生血管的血管渗透性的血管内络合物和菲霉菌渗透性的血管内渗透性的最初缺氧环境中最突出的蛋白质。我们的结果揭示了潜在的新治疗靶标，以解决缺氧诱导的病理血管生成和视网膜疾病数量的相关血管渗透性。

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