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。     

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。     

胰岛素样生长因子-1与早产儿视网膜病变

早产儿视网膜病变(ROP)是儿童主要的致盲眼病之一。氧调节和非氧调节生长因子均参与ROP的发生。血管内皮生长因子(VEGF)是一种重要的氧调节因子,其在新生血管形成中的重要作用已逐渐被认识,而非氧调节生长因子(胰岛素样生长因子-1,IGF-1)可能与早产儿脱离子宫内环境有关。本文主要讨论IGF-1和VEGF在ROPⅠ、Ⅱ期病变中的作用,以期能在早期评价个体的ROP发生倾向,及早进行干预,降低ROP发生率。     

湖南省儿童医院2010-2012年早产儿视网膜病变的发病情况及危险因素分析

早产儿视网膜病变（retinopathyofprematurity,ROP）是发生在早产儿,尤其低出生体重早产儿的一种视网膜毛细血管发育异常的双侧性眼病,是影响早产儿生存质量的主要原因之一,是世界范围内儿童致盲的主要原因,约占儿童致盲原因的6％～18％。在我国,随着围产医学的进步和新生儿监护设施的完善,早产儿成活率大大提高,ROP发生率也随之显著增高。     

抗VEGF药物玻璃体内注射治疗对早产儿视网膜病变神经系统发育的影响

早产儿视网膜病变(ROP)是以视网膜血管异常增生为主要病理特征的儿童致盲眼病。血管内皮生长因子(VEGF)是一种特异性刺激血管内皮细胞增生及新生血管形成的生长因子。早产儿视网膜局部缺血、缺氧环境促使眼内VEGF表达代偿性升高,进而诱导视网膜血管病理性生长。玻璃体内注射抗VEGF药物可抑制眼内VEGF的生物活性,从而延缓...     

我国早产儿视网膜病变特点和筛查指南

早产儿视网膜病变 (ROP)是早产儿和低体重儿发生的一种视网膜血管增生性病变 ,是世界发达国家儿童失明的首位原因。随着我国医疗水平的不断提高 ,围产医学也有了极大的发展 ,各种生命支持系统的改进 ,早产儿存活率不断提高。伴随早产儿存活率的提高 ,ROP的发生率也随之上升 ,由此造成的儿童盲目越来越多。对早产儿进行眼底检查 ,发现阈值病变并及时治疗 ,可以有效地降低 ROP的致盲率。1　ROP的流行病学特点我国大陆目前尚缺乏以人群为基础的 ROP发病率的流行病学资料。流行病学调查结果显示 ,80年代 ,在欧美国家的早产儿当中 ,ROP的…     

抗VEGF药物玻璃体内注射治疗对早产儿视网膜病变神经系统发育的影响

早产儿视网膜病变(ROP)是以视网膜血管异常增生为主要病理特征的儿童致盲眼病。血管内皮生长因子(VEGF)是一种特异性刺激血管内皮细胞增生及新生血管形成的生长因子。早产儿视网膜局部缺血、缺氧环境促使眼内VEGF表达代偿性升高, 进而诱导视网膜血管病理性生长。玻璃体内注射抗VEGF药物可抑制眼内VEGF的生物活性, 从而延缓视网膜新生血管形成, 可有效治疗ROP。然而, ROP患者常伴有血-视网膜屏障损伤, 导致视网膜微环境稳态失衡, 抗VEGF药物易透过血-视网膜屏障及血-脑屏障进入全身血液循环, 可能导致ROP患儿神经系统发育异常。目前抗VEGF药物玻璃体内注射是否影响患儿神经系统发育仍是眼科研究的热点。本文就VEGF在ROP发病机制和神经发育中的作用以及抗VEGF药物玻璃体内注射对ROP患儿神经系统发育的影响进行综述, 以期为临床合理、安全应用抗VEGF药物提供依据。     

重视早产儿视网膜病变的防治

早产儿视网膜病变(ROP)以往被称为“晶状体后纤维增生症”,是发生于早产儿和低体重儿中的视网膜血管增生性病变。ROP是发达国家儿童首位致盲原因。随着我国医疗水平的不断提高,围产医学有了较大的发展,各种生命支持系统的逐渐改进和完善,明显提高了早产儿的存活率,随之ROP发生率也相应上升,由此导致的盲童数量也不断增多,应当引起各级医疗单位的重视。因此,有必要就不同地区ROP发生率、ROP防治情况、早产儿视网膜血管发育特征、ROP患儿的视网膜组织学改变特点、ROP的国际分类及治疗时限等情况进行分析和评述。ROP发生率从某种程度上反映了国家对新生儿重症监护的救治水平和相关医疗法规健全情况。（中华眼科杂志,2005,41：289-291）     

早产儿视网膜病变危险因素研究进展

早产儿视网膜病变(retinopathy of prematurity,ROP)是一种视网膜血管增生性疾病,近年来随着医疗水平的不断提高,其发病率也显著增高,该病已成为我国儿童致盲的主要原因之一.目前其发病机制尚不清楚,认为早产、低出生体质量和吸氧是该病的三大危险因素.本文就可能引发该病的多个因素进行综述,旨在扩充ROP的病因和发病机制,为该病的防治提供理论依据.     

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.     

【In Press】 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 4-6wk 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.     

Retinopathy of prematurity: A review of pathophysiology and signaling pathways

Retinopathy of prematurity (ROP) is a vasoproliferative disorder of the retina and a leading cause of visual impairment and childhood blindness worldwide. The disease is characterized by an early stage of retinal microvascular degeneration, followed by neovascularization that can lead to subsequent retinal detachment and permanent visual loss. Several factors play a key role during the different pathological stages of the disease. Oxidative and nitrosative stress and inflammatory processes are important contributors to the early stage of ROP. Nitric oxide synthase and arginase play important roles in ischemia/reperfusion-induced neurovascular degeneration. Destructive neovascularization is driven by mediators of the hypoxia-inducible factor pathway, such as vascular endothelial growth factor and metabolic factors (succinate). The extracellular matrix is involved in hypoxia-induced retinal neovascularization. Vasorepulsive molecules (semaphorin 3A) intervene preventing the revascularization of the avascular zone. This review focuses on current concepts about signaling pathways and their mediators, involved in the pathogenesis of ROP, highlighting new potentially preventive and therapeutic modalities. A better understanding of the intricate molecular mechanisms underlying the pathogenesis of ROP should allow the development of more effective and targeted therapeutic agents to reduce aberrant vasoproliferation and facilitate physiological retinal vascular development.     

Prevention of retinopathy of prematurity

Retinopathy of prematurity (ROP) is related to oxygen-regulated vascular endothelial growth factor and to insulin-like growth factor-I. After premature birth, supplemental oxygen induces a retinal hyperoxic condition with vasoconstriction and to a definitive interruption of retinal vasculogenesis. Peripheral ischemia may stimulate retinal neovascularization and the onset of additional ROP-related complications. The natural course of the disease may result in irreversible blindness if not promptly diagnosed and attended. Recently, a significant increase in the prevalence of ROP has been observed in survival rates of preterm infants, especially in emerging-economy countries in Latin America, Asia, and Eastern Europe. This article addresses the main preventive measures in ROP.     

Pathogenese der Retinopathia praematurorum

Retinopathy of prematurity (ROP) is a vascular disease of the eye unique to preterm infants. The distinctive feature of ROP is that is an illness of the still-maturing organism. Thus, an understanding of the normal fetal development of the retina is fundamental to understanding the pathogenesis of ROP. Animal models of ROP differ in important attributes, a fact that is important for interpretation of results. However, all models have in common the finding that ROP is a biphasic disease. In the first phase, relative hyperoxia results in vaso-obliteration and vessel loss. The second phase is characterized by hypoxia-induced neovascularization resulting in retinal detachment and blindness. Oxygen-dependent vascular endothelial growth factor (VEGF) and oxygen-independent insulin-like growth factor (IGF-1) have been identified as important factors in the pathogenesis of ROP. These findings suggest new therapeutic approaches. Substitution of IGF-1 during the first phase of the disease may help prevent vessel loss, and administration of anti-angiogenic substances during the second phase may prevent pathological neovascularization.     

Inhibition of oxygen-induced retinopathy in RTP801-deficient mice

PURPOSE: Ischemic proliferative retinopathy, which occurs as a complication of diabetes mellitus, prematurity, or retinal vein occlusion, is a major cause of blindness worldwide. In addition to retinal neovascularization, it involves retinal degeneration, of which apoptosis is the main cause. A prior report has described the cloning of a novel HIF-1-responsive gene, RTP801, which displays strong hypoxia-dependent upregulation in ischemic cells of neuronal origin, both in vitro and in vivo. Moreover, inducible overexpression of RTP801 promotes the apoptotic death of differentiated neuron-like PC12 cells and increases their sensitivity to ischemic injury and oxidative stress. The purpose of the study was to examine the potential role of RTP801 in the pathogenesis of retinopathy, using RTP801-deficient mice. METHODS: Wild-type and RTP801-knockout mice were used in a model of retinopathy of prematurity (ROP). Their retinas were collected at postnatal day (P)14 and P17. They were examined by fluorescein angiography and by analysis of VEGF expression, neovascularization, and apoptosis. RESULTS: The expression of RTP801 was induced in the wild-type retina after hypoxia treatment. The retinal expression of VEGF after transfer to normoxic conditions was similarly upregulated in both wild-type and knockout mice. Nevertheless, the retinas of the RTP801-knockout mice in an ROP model showed a significant reduction in retinal neovascularization (P < 0.0001) and in the number of apoptotic cells in the inner nuclear layer (P < 0.0001). CONCLUSIONS: In the absence of RTP801 expression, development of retinopathy in the mouse model of ROP was significantly attenuated, thus implying an important role of RTP801 in the pathogenesis of ROP.     

早产儿视网膜病变的神经视网膜发育研究

早产儿视网膜病变(retinopathy of prematurity,ROP)被视为引起视觉受损的重要疾病之一,它的主要临床特点是视网膜周边血管异常,包括大片无血管灌注区及异常新生血管形成。大量研究证明ROP会影响视网膜光感受器细胞的分化和成熟,且对视杆细胞影响较视锥细胞显著,后期还大多引起屈光不正、斜视、弱视等一系列的视功能异常表现,具体机制尚不明确。经治疗后即使视网膜本身血管增殖病变消失,但ROP光感受器细胞的异常发育及由此导致的视功能障碍会持续存在。目前临床上对视网膜功能的最佳评估手段主要是视觉电生理,尤其是闪光视网膜电流图(f-ERG)可反映神经节细胞以前整个视网膜的功能状态,对评估视网膜的感光细胞功能具有独特的意义。本文主要针对ROP对神经视网膜发育(主要是光感受器细胞)的影响及其相关机制、ROP后期视功能改变及相关机制进行综述,从而指导我们寻求更佳的治疗方法。     

早产儿视网膜病变研究进展

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,重者可以引起视网膜脱离而导致永久性失明。近年来,随着围产医学的进步,早产儿成活率逐渐增加,相应ROP发生率也呈增加趋势。由于其后果严重,对患儿及其家庭造成巨大伤害,ROP也日益引起人们的重视。目前ROP的确切病因仍未明确,真正的发病机制尚不十分清楚,亦缺乏有效的预防措施。本文从ROP的发病因素、发病机制及干预措施三方面对其新近研究进展作一综述。