Concurrent Physiological and Pathological Angiogenesis in Retinopathy of Prematurity and Emerging Therapies.
Concurrent Physiological and Pathological Angiogenesis in Retinopathy of Prematurity and Emerging Therapies.
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DOI：
10.3390/ijms22094809
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发表时间：
2021-05-01
影响因子：
5.6
通讯作者：
Li W
中科院分区：
文献类型：
--
作者：
Dai C;Webster KA;Bhatt A;Tian H;Su G;Li W
早产儿视网膜病变（ROP）是一种影响早产儿的眼部血管疾病，其特征是病理性视网膜新生血管（RNV）、视网膜血管扩张和弯曲，以及视网膜或玻璃体出血，可导致视网膜脱离、视力损害和失明。与其他新生血管疾病相比，ROP是独特的，因为在发育中的视网膜中存在持续和并发的生理性和病理性血管生成。虽然目前该疾病的治疗方法是激光或冷冻疗法，但抗血管内皮生长因子（VEGF）药物已被广泛研究，但由于安全性问题，它们会对发育中的视网膜的生理性血管生成产生负面影响，因此未在美国获得批准。理想的治疗策略是选择性地抑制病理性而非生理性血管生成。我们的研究小组最近描述了一种新的策略，通过靶向分泌颗粒蛋白III (Scg3)，一种疾病限制性血管生成因子，选择性和安全地减轻ROP动物模型中的病理性RNV。抗scg3治疗的临床前概况显示，下一代针对ROP适应症的疾病靶向抗血管生成治疗具有很高的潜力。本文综述了新生儿视网膜血管的发育、ROP的发病机制及其潜在的分子机制，包括不同的动物模型，并概述了目前和新兴的治疗方法。
Retinopathy of prematurity (ROP) is an ocular vascular disease affecting premature infants, characterized by pathological retinal neovascularization (RNV), dilated and tortuous retinal blood vessels, and retinal or vitreous hemorrhages that may lead to retinal detachment, vision impairment and blindness. Compared with other neovascular diseases, ROP is unique because of ongoing and concurrent physiological and pathological angiogenesis in the developing retina. While the disease is currently treated by laser or cryotherapy, anti-vascular endothelial growth factor (VEGF) agents have been extensively investigated but are not approved in the U.S. because of safety concerns that they negatively interfere with physiological angiogenesis of the developing retina. An ideal therapeutic strategy would selectively inhibit pathological but not physiological angiogenesis. Our group recently described a novel strategy that selectively and safely alleviates pathological RNV in animal models of ROP by targeting secretogranin III (Scg3), a disease-restricted angiogenic factor. The preclinical profile of anti-Scg3 therapy presents a high potential for next-generation disease-targeted anti-angiogenic therapy for the ROP indication. This review focuses on retinal vessel development in neonates, the pathogenesis of ROP and its underlying molecular mechanisms, including different animal models, and provides a summary of current and emerging therapies.
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