Hypoxia-Inducible Factor Inhibitors Derived from Marine Products Suppress a Murine Model of Neovascular Retinopathy
Hypoxia-Inducible Factor Inhibitors Derived from Marine Products Suppress a Murine Model of Neovascular Retinopathy
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DOI：
10.3390/nu12041055
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发表时间：
2020-04
期刊：
影响因子：
5.9
通讯作者：
Chiho Shoda;Yukihiro Miwa;K. Nimura;K. Okamoto;S. Yamagami;K. Tsubota;T. Kurihara
中科院分区：
文献类型：
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作者：
Chiho Shoda;Yukihiro Miwa;K. Nimura;K. Okamoto;S. Yamagami;K. Tsubota;T. Kurihara
新生血管性视网膜变性疾病是发达国家致盲的主要原因。抗血管内皮生长因子（VEGF）治疗是目前治疗这些疾病的常用方法。然而，最近的报道表明，眼睛中VEGF的长期抑制与脉络膜视网膜萎缩有关。因此，视网膜稳态需要生理量的VEGF。缺氧诱导因子（Hypoxia-inducible Factor，HIF）是位于VEGF上游的一种转录因子。我们以前报道过缺氧诱导因子调节氧诱导视网膜病变和激光诱导脉络膜新生血管的小鼠模型视网膜中的病理性血管生成。大多数已知的HIF抑制剂是抗癌剂，其在临床应用中可能具有全身性不良反应;因此，需要更安全且侵入性更小的HIF抑制剂。本研究对海产品，尤其是鱼类成分进行筛选，发现6种鱼类具有HIF抑制作用。其中，在鼠氧诱导的视网膜病模型中，通过抑制HIF表达，施用圆圆片成分显著抑制视网膜新生血管簇。这些结果表明，特定的鱼类成分可以作为视网膜新生血管疾病的抗血管生成剂。
Neovascular retinal degenerative diseases are the leading causes of blindness in developed countries. Anti-vascular endothelial growth factor (VEGF) therapy is commonly used to treat these diseases currently. However, recent reports indicate that long term suppression of VEGF in the eye is associated with chorioretinal atrophy. Therefore, a physiological amount of VEGF is required for retinal homeostasis. Hypoxia-inducible factor (HIF) is a transcriptional factor upstream of VEGF. We previously reported that HIF regulated pathological angiogenesis in the retina of murine models of oxygen-induced retinopathy and laser-induced choroidal neovascularization. Most of the known HIF inhibitors are anti-cancer agents which may have systemic adverse effects in for clinical use; thus, there is a need for safer and less invasive HIF inhibitors. In this study, we screened marine products, especially fish ingredients, and found that six species of fish had HIF inhibitory effects. Among them, administration of Decapterus tabl ingredients significantly suppressed retinal neovascular tufts by inhibiting HIF expression in a murine oxygen-induced retinopathy model. These results indicate that particular fish ingredients can act as anti-angiogenic agents in retinal neovascularization diseases.