Redox Mechanisms in Pathological Angiogenesis in the Retina: Roles for NADPH Oxidase
Redox Mechanisms in Pathological Angiogenesis in the Retina: Roles for NADPH Oxidase
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DOI：
10.2174/1381612821666151029111127
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发表时间：
2015-01-01
影响因子：
3.1
通讯作者：
Dusting, Gregory J.
中科院分区：
文献类型：
--
作者：
Chan, Elsa C.;Liu, Guei-Sheung;Dusting, Gregory J.
视网膜中的病理性血管生成是潜在致盲眼病中严重视力丧失的主要原因，这些疾病包括增殖性糖尿病视网膜病变、早产儿视网膜病变和湿性年龄相关性黄斑变性。缺氧被认为是病理性血管生成的驱动因素，而缺氧诱导因子（HIF）和血管内皮生长因子（VEGF）等转录因子是这些过程中的关键介质。目前的治疗方法采用激光光凝或玻璃体内注射 VEGF 治疗抗体，以阻止无血管玻璃体腔中渗漏血管的生长并恢复视力。然而，所有这些治疗方法都受到功效低或变化多端以及需要频繁给予的治疗的不便、风险和经济负担的限制。因此，缺乏非侵入性和有效的治疗方法促使人们寻找替代策略。我们一直对活性氧（ROS）的作用很感兴趣，例如超氧化物和过氧化氢，当它们在细胞内以低浓度产生时，可以充当调节生理和病理血管生成的第二信使。越来越多的证据表明 NADPH 氧化酶依赖性 ROS 参与 HIF 和 VEGF 血管生成信号通路的调节。通过操纵这种氧化还原机制来抑制视网膜中的病理性新生血管形成似乎是治疗增殖性新生血管眼病的一种有吸引力且可临床转化的治疗策略。在这里，我们简要概述了 NADPH 氧化酶在涉及 HIF 和 VEGF 的传感和调节过程中的作用，这些过程有助于视网膜病理性血管生成的发展。
Pathological angiogenesis in the retina is a leading cause of serious vision loss in potentially blinding eye diseases, including proliferative diabetic retinopathy, retinopathy of prematurity and the wet form of age-related macular degeneration. Hypoxia is thought to be the driver of pathological angiogenesis, and transcription factors such as hypoxia-inducible factor (HIF) and vascular endothelial growth factor (VEGF) are key mediators in these processes. Current treatments employ either laser photocoagulation or intravitreal injection of therapeutic antibodies for VEGF, in order to arrest the growth of leaky blood vessels in the avascular vitreous cavity and to restore visual acuity. However, all such therapeutic approaches are limited by low or variable efficacy, and the inconvenience, risk and financial burden of such treatments, which need to be given frequently. The lack of non-invasive and efficacious therapy has therefore driven the search for alternative strategies. We have been interested in the roles of reactive oxygen species (ROS), such as superoxide and hydrogen peroxide, which when produced intracellularly at low concentration can act as second messengers to regulate physiological and pathological angiogenesis. Accumulating evidence suggests NADPH oxidase-dependent ROS are involved in regulation of the angiogenic signalling pathways of HIF and VEGF. Suppressing pathological neovascularisation in the retina by manipulating such redox mechanisms appears to be an attractive and clinically translatable therapeutic strategy to treat proliferative neovascular eye diseases. Here we provide a brief overview of the roles of NADPH oxidase in the sensing and regulation processes involving HIF and VEGF that contribute to the development of pathological angiogenesis in the retina.