抗VEGF药物治疗早产儿视网膜病变的研究进展

早产儿视网膜病变(retinopathy of prematurity,ROP)是目前全世界儿童致盲的主要原因之一[1]。以往对于阈值期和高危阈值前期的ROP采用激光或冷凝治疗,因激光和冷凝术均是破坏性的,不可避免地导致周边视野永久丧失,且并发症较多,术后仍有部分患儿病情无法控制,最终视力完全丧失。因此需要寻找新的治疗方法,近年来有较多的临床数据表明,玻璃体内注射抗血管内皮生长因子(anti-vascular endothelial growth factor,anti-VEGF)治疗ROP是一种有效的治疗方法。我们将对抗VEGF药物在ROP治疗的研究进展进行近期的文献综述。     

雌激素干预早产儿视网膜病变的研究进展

早产儿视网膜病变(ROP)是一种以视网膜新生血管为主要病理改变的疾病,是儿童致盲的主要原因之一。目前主要采取激光或手术治疗,损伤较大且效果不理想,因此寻找有效的药物途径来预防ROP的发生成为研究热点。血管内皮生长因子(VEGF)是一种已知的促新生血管生成物质,在ROP的发病过程中起关键作用,雌激素通过调控VEGF减少新生血管生成,从而防止ROP的发生。本文将围绕早产儿视网膜病变新生血管,VEGF以及雌激素三者之间的关系进行综述。     

早产儿视网膜病变发病机制及药物治疗的研究进展

早产儿视网膜病变(ROP)是发生于早产儿和低体重儿中的视网膜血管增生性病变,是儿童致盲的主要原因之一。研究ROP发生的危险因素、发病机制及药物干预治疗,对降低ROP的发生率和致盲率有着极其重要意义。近年来随着新生血管研究的深入,新生血管抑制剂用于预防及治疗ROP的研究也越来越多,本文拟对近年来有关ROP上述研究进展作一综述。     

早产儿视网膜病变视觉电生理研究进展

早产儿视网膜病变（ROP）是指可发生于未成熟儿的以视网膜血管异常增生为特征的视网膜血管疾病,是造成儿童视力损害的主要原因之一。ROP虽以视网膜血管发育异常为主要临床特征,但临床观察及动物实验证实,ROP同样影响视网膜视神经的发育,引起视网膜和视神经功能的异常,出现视网膜电图（ERG）暗视视杆反应、暗视振荡电位、多焦视网膜电图（mfERG）的异常,此外,对患儿屈光系统的发育也产生不同程度的影响。就ROP动物模型及ROP患者视觉电生理的特点及屈光系统的异常发育与病变之间的关系进行综述。     

早产儿视网膜病变研究进展

早产儿视网膜病变(ROP)是一种增殖性视网膜病变,是世界范围内儿童致盲的主要原因,本文阐述了ROP的发病机制、危险因素、诊断、治疗及近年新进展。     

早产儿视网膜病变的研究进展

早产儿视网膜病变（retinopathyofprematurity）以往称之为晶状体后纤维增生症（retrolentalfibroplasia）本病几乎全发生在出生时体重不足1500G，并曾在出生后10天内接受过高浓度吸氧治疗的早产儿．1942年由Terry[1]首先报道，他发现本清的显著特点是，早产儿晶体后有白色纤维组织，由此而命名．后来的研究表明，本病除侵犯早产儿外，还与吸高浓度氧有关．直至1984年，世界眼科学者们才正式定名为早产地视网膜病变[2]．1．早产儿视网膜病变的发病机理近年来，尽管这方面的研究取得了一些研究，但病理机制的研究尚无定论．胚胎4个月以前，…     

早产儿视网膜病变模型研究进展

目前,早产儿视网膜病变(retinopathy of prematurity,ROP)已经成为世界范围内儿童致盲的重要原因,约占儿童致盲原因的6%～18%。防治ROP以改善早产儿的生存质量已成为全球关注的焦点。因此,建立合适的视网膜新生血管动物模型已成为探讨视网膜新生血管的发生机制并评估其药物治疗效果的重要手段。本文对用各种模型模拟ROP的发生过程进行综述。     

早产儿视网膜病变临床分析

早产儿视网膜病变是体重不足的早产儿因供氧过度，视网膜血管异常增生的一类增生性视网膜病变，是目前儿童致盲的主要原因之一。现将我院门诊1999年至2002年诊治的15例患儿的临床情况分析如下。     

感染/炎症在早产儿视网膜病变中的作用

感染/炎症是早产的重要启动因素,同时感染也是早产儿常见的并发症。近来,临床研究提示早产儿视网膜病变(retinopathy of prematurity,ROP)与新生儿或母体的感染/炎症相关;基础研究也发现炎症可影响视网膜血管的正常发育,参与调控视网膜新生血管的形成。了解感染/炎症在ROP中的可能作用,对于ROP的早期诊断和防治有重要意义。本文就感染/炎症与ROP的关系及相关的作用机制进行综述。     

早产儿视网膜病变的研究进展

早产儿视网膜病变(retinopathy of prematurity,ROP)是早产儿尤其是伴有低体重儿发生的一种视网膜毛细血管发育异常化的双侧性眼病,表现为视网膜缺血,新生血管形成和增生性视网膜病变,重症者可引起视网膜脱离而导致永久性失明。ROP已经成为我国儿童致盲的原因之一。本文着重阐述了早产儿视网膜病变的发病机制、诊断和治疗的最新进展。     

早产儿视网膜病变影响因素调查

目的：分析早产儿视网膜病变发生情况及其影响因素。
　　方法：选取2012-05/2013-05间在我院眼科出生的103例早产儿作为研究对象,筛查早产儿视网膜病变发生率及影响因素。
　　结果：早产儿视网膜病变检出率为11.7%,多因素Logistic回归分析显示胎龄、吸氧浓度、出生体质量、机械通气、吸氧时间、贫血、颅内出血均为早产儿视网膜病变的危险因素(P<0.05)。
　　结论：低出生体质量的早产儿在吸氧浓度等因素上都与早产儿视网膜病变的发生有显著关系。     

The progress of prophylactic treatment in retinopathy of prematurity

Retinopathy of prematurity (ROP) is a retinal vascular disorder frequently found in premature infants. Different therapeutic strategies have been developed to treat ROP. However, there are still many children with ROP suffering by severe limitations in vision or even blindness. Recently, ROP has been suggested to be caused by abnormal development of the retinal vasculature, but not simply resulted by retinal neovascularization which takes about 4 to 6wk after birth in premature infants. Thus, instead of focusing on how to reduce retinal neovascularization, understanding the pathological changes and mechanisms that occur prior to retinal neovascularization is meaningful, which may lead to identify novel target(s) for the development of novel strategy to promote the healthy growth of retinal blood vessels rather than passively waiting for the appearance of retinal neovascularization and removing it by force. In this review, we discussed recent studies about, 1) the pathogenesis prior to retinal neovascularization in oxygen-induced retinopathy (OIR; a ROP in animal model) and in premature infants with ROP; 2) the preclinical and clinical research on preventive treatment of early OIR and ROP. We will not only highlight the importance of the mechanisms and signalling pathways in regulating early stage of ROP but also will provide guidance for actively exploring novel mechanisms and discovering novel treatments for early phase OIR and ROP prior to retinal neovascularization in the future.     

精氨酸-谷氨酰胺在幼鼠早产儿视网膜病变模型中的应用(英文)

目的:观察精氨酸-谷氨酰胺(Arg-Gln)对早产儿视网膜病变动物模型视网膜新生血管的抑制作用。方法:48只7日龄的C57BL/6J新生鼠暴露在750mL/L高氧环境中5d,然后回到正常空气中建立早产儿视网膜病变的动物模型。在鼠龄12d时实验组(36只)新生鼠每天两次腹腔注射Arg-Gln(剂量分别为1.0,3.0,5.0g/kg,每组12只),连续注射5d;对照组(12只)每天两次腹腔注射PBS,连续5d。所有小鼠均于17d处死,视网膜铺片,ADP酶染色观察视网膜血管情况。HE染色,在光学显微镜下观察并计数突破视网膜内界膜的血管内皮细胞细胞核数目。Real-time RT-PCR方法测量每组视网膜VEGF mRNA水平。结果:与对照组相比,实验组以剂量依赖方式无灌注区面积和新生血管团逐渐减少;实验组中最大剂量组[5.0g/(kg·d)]突破内界膜的内皮细胞细胞核数目比对照组大约减少75%(P<0.01);实验组视网膜VEGF mRNA水平与对照组相比明显下降。结论:Arg-Gln能够有效抑制早产儿视网膜病变动物模型视网膜新生血管的生成,可能为临床提供一种预防和治疗早产儿视网膜病变安全有效的新方法。     

Effect of the dipeptide Arg-Gln on retinopathy of prematurity in mice

AIM: To investigate the effect of the dipeptide Arg-Gln on retinal neovascularization of retinopathy of prematurity (ROP) in the oxygen-induced retinopathy (OIR) animal model. METHODS: Forty-eight 7-day-old C57BL/6J mice were exposed to 750mL/L oxygen for 5 days and then to normal situation to produce the murine model of oxygen-induced retinopathy (OIR). All mice received twice daily intra- peritoneal injections of PBS or the dipeptide Arg-Gln (1.0, 3.0, 5.0g/kg per day), starting on postnatal day 12 and continuing till postnatal day 17. Experimental groups (36 mice, 12 in each group) received Arg-Gln, while the control group (12 mice) received PBS. All mice were executed at postnatal day 17. The changes of retinal vessels of mice were observed by ADPase histochemical technique and HE staining was used to count preretinal neovascular nuclei. RNA was isolated from retinas of 28 mice (7 in each group) selected at random and VEGF mRNA level of each group was measured by real-time RT-PCR. RESULTS: Neovascularization reduced in retinas of the dipeptide Arg-Gln treated group in a dose-dependent manner. Compared with control group, experimental group had diminished non-perfusion area and neovascular tufts in retinal flatmount. The number of the endotheliocyte nuclei of new vessels extending from retina to vitreous was significantly less in the eyes of the experimental group than in control group. Arg-Gln at 5g/kg per day reduced preretinal neovascularization by about 75% (P <0.01). There was a significant reduction in VEGF mRNA at the 17^th day in Arg-Gln treated group compared with control group(P ＜0.01). CONCLUSION: Arg-Gln dramatically inhibits retinal angiogenesis in OIR and this effect is associated with a reduction in retinal VEGF mRNA level. It appears to be a safe way to prevent and treat some neovascular retinal diseases including retinopathy of prematurity.     

PTK787抑制早产儿视网膜病变大鼠模型新生血管的形成

目的探讨受体酪氨酸激酶亚群抑制剂PTK787对早产儿视网膜病变(retinopathy of prematurity,ROP)新生血管形成的抑制作用。方法建立波动氧(体积分数80%和10%氧浓度24h反复交替)诱导的SD大鼠ROP模型。67只新生SD大鼠随机设立对照组(22只)、模型组(22只)、治疗组(23只,腹腔注射PTK78750mg.kg-1);分别于第12天和第17天,每组随机抽取8只新生鼠,一侧眼球采用ADP酶组织化学法进行视网膜铺片,观察视网膜血管改变;另一侧眼球视网膜组织切片观察并计数突破视网膜内界膜的血管内皮细胞核数目。结果波动氧可成功诱导SD新生大鼠ROP模型,PTK787可抑制氧诱导新生鼠视网膜病变模型新生血管的形成。第12天和第17天时,模型组视网膜ADP酶组织化学铺片,均较对照组血管分布、密度改变明显;而治疗组视网膜铺片血管密度较模型组明显下降。第17天突破视网膜内界膜的血管内皮细胞核计数结果显示,给氧模型组31.360±4.543与正常对照组1.700±1.216比较,差异有显著统计学意义(t=-56.414,P<0.001)。治疗组6.800±2.107与模型组相比,血管内皮细胞核数显著减少(t=-43.869,P<0.001)。结论 PTK787可以抑制视网膜新生血管的形成,有望成为治疗ROP的有效途径。     

长链非编码RNA在早产儿视网膜病变中的作用研究进展

在围产医学水平不断提升的条件下,早产儿存活率明显提升,加之二胎政策的开放以及辅助生殖技术的进步,高龄产妇和多胎妊娠相对增多,早产儿视网膜病变(retinopathy of prematurity,ROP)作为常见的早产儿缺氧性疾病也呈现出高发病率趋势。目前普遍认为早产儿的发病原因为缺血缺氧,但其发生发展机制仍有待深入研究。近年来,关于长链非编码RNA(long non-coding RNA,lncRNA)在ROP及其他视网膜新生血管性疾病中的作用已有大量的相关研究。本文旨在综述lncRNA的表达与调控对ROP发生发展的影响,为临床控制与治疗ROP提供理论基础。     

Management of retinopathy of prematurity

Seventeen patients with symmetrical stage 3 retinopathy of prematurity (ROP) and plus disease as described in the International Classification of ROP had one eye randomized to cryotherapy and the other to control. Seventy-seven percent of the patients were under 1000 grams at birth and females outnumbered males by a 2 to 1 ratio. The average chronologic age at which cryotherapy was performed was three months. Twelve of seventeen treated eyes (71%) showed resolution of the ROP and 10 of 17 untreated eyes (59%) became significantly worse. However, only five patients had improvement in the treated eye and progression in the untreated eye, a number too small to provide statistical significance. Six eyes with Stage IV ROP were operated by encircling scleral buckling techniques because of total retinal detachment secondary to peripheral traction and cicatrization arising from the ridge. In five patients the unoperated eye had already developed a retrolental membrane, and in one patient bilateral detachments were present. Five of the six operated retinas were reattached.     

直接肾素阻滞剂Aliskiren预防早产儿视网膜病变

肾素作为肾素-血管紧张素系统（ｒｅｎｉｎ-ａｎｇｉｏｔｅｎｓｉｎｓｙｓｔｅｍ,ＲＡＳ）中上游生长因子,对ＲＡＳ链起着特异性限速的作用。在早产儿视网膜病变等缺血性视网膜病变中,ＲＡＳ上调,视网膜ＲＡＳ被激活,刺激血管内皮生长因子等上调,导致血管渗漏、血管内皮细胞增生和新生血管形成等血管病理性改变。直接肾素抑制剂Ａｌｉｓｋｉｒｅｎ作为阻断ＲＡＳ的新途径,在防止和减弱病理性血管生成的过程中发挥了明显作用。Ａｌｉｓｋｉｒｅｎ的应用有望成为早产儿视网膜病变的预防及治疗途径。     

Cryotherapy for retinopathy of prematurity

With the rapid progress in neonatology saving more lives of very immature infants, the occurrence of retinopathy of prematurity or retrolental fibroplasia has increased although most cases spontaneously resolve, severe visual damage and blindness still occur. The progressive case of retinopathy is a dilemma for ophthalmologists consulting in the intensive care nursery. The Japanese have been pursuing modalities of treatment of the acute case, but there are few reported cases in the United States and Canada. Four cases of retinopathy of prematurity treated by cryotherapy are presented with follow-up. This is done in an effort to stimulate further reporting and consideration of treatment of such cases.