新的早产儿视网膜病变动物模型的建立

Retinopathy of prematurity (ROP) is a major cause of blindness in children all over the world, which characterized by onset of vascular abnormalities in the developing retina of premature or low birth weight infants. ROP is a complex condition in which various factors, such as low gestational age, low birth weight, increased oxygenation, sepsis/inflammation, are involved. The pathogenesis of ROP and exact mechanisms are still unclear, which restricted its effective prevention and treatment. .However, there are no ROP animal model in basic research. Current animal models widely used in ROP investigation are oxygen-induced retinopathy models(OIR). But manifestations of these models do not mimic the real pathogenesis status of human ROP patients. Retinal neovascularization regressed in a few days, and retinal hemorrhage, retinal detachment can rarely be observed. Thus, in the present study, we try to integrate "preterm birth murine infants" into research for the first time, and study the developing features of retina in preterm birth murine infants. We then investigate the effects of various risk factors, such as high oxygen, infection/inflammation, metabolic acidosis on retinas of preterm birth infants, and try to establish a novel animal model of ROP based on appropriate risk factors and experiment condition. In addition, a comprehensive comparison will be made betweem the new model and traditional OIR models, anti-VEGF intevention will also be included..The novel ROP model is expected to be more specific to ROP, which exhibit similar features in ROP clinic such as retinal hemorrhage, retinal detachment and prolonged time course of retinal neovascularization and so on. In spite of exploring a new animal model, a "multi-hit" theory in ROP pathogenesis will be established.

早产儿视网膜病变（ROP）为儿童首位致盲原因，是与小胎龄、低体重、吸氧以及感染/炎症等相关的视网膜血管异常增生性疾病，迄今发病机制欠清。目前广泛用于ROP研究的动物模型为氧诱导视网膜病变模型，其特异性差，采用高浓度氧单一因素处理,形成的新生血管消退快,且不发生视网膜脱离等ROP常见并发症,因此建立一种更贴近人类ROP临床本质的新动物模型势在必行。本项目首次将"早产"这一关键因素引入研究，在深入探讨早产幼鼠视网膜发育动态规律和特点的基础上，选择与临床类似的高氧、感染/炎症和酸中毒等多种危险因素进行干预，采用病理学指标和活体眼底图像评价体系，综合遴选适合的危险因素和实验条件，旨在建立一种新的ROP动物模型，并对比其与传统模型的差别及对干预治疗的反应特征。预期新模型中视网膜新生血管持续时程增加，并具视网膜出血或脱离等典型的临床特征。若此新的实验平台创建,将为阐明ROP发病机制奠定坚实基础。

产儿视网膜病变（ ROP）为儿童首位致盲原因，是与小胎龄、低体重、吸氧以及感染/炎症等相关的视网膜血管异常增生性疾病，迄今发病机制欠清。目前广泛用于 ROP研究的动物模型为氧诱导视网膜病变模型（OIR），其采用高浓度氧单一因素处理，存在特异性差，形成的新生血管消退快，且不发生视网膜脱离等 ROP 常见并发症,因此建立一种更贴近人类 ROP 临床本质的新动物模型势在必行。本研究组将“早产”这一关键因素引入研究，深入探讨了早产幼鼠视网膜发育动态规律和特点，并在此基础上，结合高氧、感染/炎症等多种危险因素进行干预，建立了新的可以更好模拟临床疾病的动物模型，为阐明ROP发病机制奠定了基础。在研究中通过使用多种方式诱导早产，结合视网膜铺片、免疫组织化学染色、视觉电生理检查等方法，探讨早产和多种因素在视网膜发育中对结构和功能的影响；将采用多种复合因素建立了新模型与传统模型进行系统的组织学和功能学对比研究；并且根据研究中发现的关键问题进行了拓展研究，主要使用药物清除或抑制炎症、骨髓移植、细胞共培养、迁移成管分析，并结合多种分子检测技术等，深入研究了感染/炎症作为重要的因素在ROP的发生发展中的作用及其机制。本项目研究结果为ROP的研究提供了新的平台，并深入揭示了炎症因素的作用机制，为ROP的防治提供了新策略。