State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, Guangdong Province, China.
J Pineal Res. 2018 May;64(4):e12473. doi: 10.1111/jpi.12473. Epub 2018 Mar 8.
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.
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），在严重情况下可能导致失明。目前，抗血管内皮生长因子（VEGF）治疗是 ROP 的主要治疗方法，但费用高昂，可能会引起严重的并发症。先前的研究表明，褪黑素对新生大鼠缺氧诱导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 进展过程中是否具有抗血管生成和神经胶质保护作用尚不清楚。因此，本研究旨在探讨褪黑素对氧诱导的视网膜病变（OIR）小鼠视网膜 RNV 和神经胶质的影响。结果表明，褪黑素治疗可减少 OIR 小鼠视网膜血管渗漏。此外，褪黑素治疗组小鼠视网膜新生血管和无血管区面积、视网膜前新生血管细胞核数以及新生血管区内增生性血管内皮细胞数均显著减少。在氧诱导损伤后，星形胶质细胞密度降低，同时星形胶质细胞形态和功能发生改变，视网膜小胶质细胞也被激活，炎症因子水平升高。然而，这些病理过程均被褪黑素治疗所阻碍。此外，HIF-1α-VEGF 通路在 OIR 小鼠视网膜中被激活，但在褪黑素治疗的 OIR 小鼠视网膜中被抑制。综上所述，褪黑素通过抑制 HIF-1α-VEGF 通路，防止病理性新生血管形成，保护神经胶质细胞，并发挥抗炎作用，这表明褪黑素可能成为 ROP 的一种有前途的治疗药物。
