Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of HIF-1α-VEGF pathway in oxygen-induced retinopathy mice
Melatonin attenuated retinal neovascularization and neuroglial dysfunction by inhibition of HIF-1α-VEGF pathway in oxygen-induced retinopathy mice
复制标题
褪黑素通过抑制氧诱导视网膜病变小鼠的 HIF-1 α-VEGF 通路来减轻视网膜新生血管形成和神经胶质细胞功能障碍
DOI：
10.1111/jpi.12473
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发表时间：
2018-05-01
影响因子：
10.3
通讯作者：
Liang, Xiaoling
中科院分区：
文献类型：
--
作者：
Xu, Yue;Lu, Xi;Liang, Xiaoling
早产儿视网膜病变（ROP）是一种视网膜病变，其特征是在接受高浓度氧气治疗的早产儿中发生视网膜新生血管（RNV），严重时可能导致失明。目前，抗VEGF治疗是ROP的主要治疗方法，但其费用昂贵且可能引起严重并发症。研究表明褪黑素对缺氧诱导的新生大鼠视网膜神经节细胞死亡具有神经保护作用。然而，褪黑激素是否在ROP的进展中具有抗血管生成和神经胶质保护作用仍不清楚。因此，本研究旨在探讨褪黑素对氧诱导视网膜病变（OIR）小鼠视网膜神经元和神经胶质细胞的影响。结果显示，在褪黑激素治疗后，OIR小鼠的视网膜血管渗漏减少。此外，视网膜新生血管和无血管区的大小，视网膜前新生血管细胞核的数量，以及新生血管区域内增殖的血管内皮细胞的数量显着减少褪黑激素治疗的小鼠。氧损伤后，星形胶质细胞密度降低，并伴有形态和功能的改变。此外，视网膜小胶质细胞也被激活。同时，炎症因子水平升高。然而，这些病理过程都受到褪黑素治疗的阻碍。此外，HIF-1 α-VEGF通路在OIR小鼠视网膜中被激活，但在褪黑激素处理的OIR小鼠视网膜中被抑制。结论：褪黑素可通过抑制OIR视网膜中HIF-1 α-VEGF通路抑制视网膜新生血管的形成，保护神经胶质细胞，发挥抗炎作用，提示褪黑素可能是一种有前景的治疗ROP的药物。
Retinopathy of prematurity (ROP) is a retinopathy characterized by retinal neovascularization (RNV) occurring in preterm infants treated with high concentrations of oxygen and may lead to blindness in severe cases. Currently, anti-VEGF therapy is a major treatment for ROP, but it is costly and may cause serious complications. The previous study has demonstrated that melatonin exerted neuroprotective effect against retinal ganglion cell death induced by hypoxia in neonatal rats. However, whether melatonin is anti-angiogenic and neuroglial protective in the progression of ROP remains unknown. Thus, this study was to investigate the effect of melatonin on RNV and neuroglia in the retina of oxygen-induced retinopathy (OIR) mice. The results showed a reduction in retinal vascular leakage in OIR mice after melatonin treatment. Besides, the size of retinal neovascular and avascular areas, the number of preretinal neovascular cell nuclei, and the number of proliferative vascular endothelial cells within the neovascular area were significantly decreased in mice treated with melatonin. After oxygen-induced injury, the density of astrocytes was decreased, accompanied by morphologic and functional changes of astrocytes. Besides, retinal microglia were also activated. Meanwhile, the levels of inflammatory factors were elevated. However, these pathologic processes were all hindered by melatonin treatment. Furthermore, HIF-1 alpha-VEGF pathway was activated in the retina of OIR mice, yet was suppressed in melatonin-treated OIR mice retinas. In conclusion, melatonin prevented pathologic neovascularization, protected neuroglial cells, and exerts anti-inflammation effect via inhibition of HIF-1 alpha-VEGF pathway in OIR retinas, suggesting that melatonin could be a promising therapeutic agent for ROP.