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‐1α‐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‐1α‐VEGF pathway in OIR retinas, suggesting that melatonin could be a promising therapeutic agent for ROP.

中文翻译：

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褪黑素通过抑制氧气诱导的视网膜病变小鼠中的HIF-1α-VEGF途径来减轻视网膜新血管形成和神经胶质功能障碍

早产儿视网膜病（ROP）是一种视网膜病，其特征是在接受高浓度氧气治疗的早产儿发生视网膜新血管形成（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，但费用昂贵且可能引起严重的并发症。先前的研究表明褪黑素对新生大鼠缺氧所致的视网膜神经节细胞死亡具有神经保护作用。然而，褪黑素在ROP进程中是否具有抗血管生成作用和神经胶质保护作用尚不清楚。因此，本研究旨在研究褪黑激素对氧诱导性视网膜病变（OIR）小鼠视网膜中RNV和神经胶质细胞的作用。结果表明，褪黑激素治疗后，OIR小鼠的视网膜血管渗漏减少。除了，褪黑素治疗的小鼠的视网膜新血管和无血管区域的大小，视网膜前新血管细胞核的数目以及新生血管区域内增殖性血管内皮细胞的数目均显着减少。氧致损伤后，星形胶质细胞密度降低，伴随着星形胶质细胞形态和功能的改变。此外，视网膜小胶质细胞也被激活。同时，炎症因子水平升高。但是，这些病理过程均受到褪黑激素治疗的阻碍。此外，HIF-1α-VEGF通路在OIR小鼠的视网膜中被激活，但在褪黑素治疗的OIR小鼠的视网膜中被抑制。总之，褪黑素可预防病理性新血管形成，保护神经胶质细胞，