Melatonin protects inner retinal neurons of newborn mice after hypoxia-ischemia
Melatonin protects inner retinal neurons of newborn mice after hypoxia-ischemia
复制标题
褪黑素对缺氧缺血后新生小鼠视网膜内神经元的保护作用
DOI：
10.1111/jpi.12716
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发表时间：
2021-04-26
影响因子：
10.3
通讯作者：
Liang, Xiaoling
中科院分区：
文献类型：
--
作者：
Huang, Rong;Xu, Yue;Liang, Xiaoling
早产儿视网膜病变是一种与视网膜缺氧缺血相关的视力威胁疾病，可导致视网膜神经元死亡和慢性神经元变性。在本研究中，我们采用氧致视网膜病变小鼠模型模拟视网膜缺氧缺血表型，进一步研究褪黑素对新生儿视网膜神经元的神经保护作用。褪黑素有助于维持相对正常的视网膜内部结构和厚度，并通过挽救视网膜神经节和双极细胞以及水平和无突神经元免于凋亡，保护无血管区域的视网膜内部神经元群。同时，褪黑素恢复了视觉功能障碍，这反映在a波、b波和振荡电位的振幅和隐式时间的改善上。此外，褪黑素治疗后，低氧缺血反应中cleaved caspase-3和Bax蛋白水平升高以及Bcl-2蛋白水平降低。此外，褪黑素增加BDNF和下游磷酸化- trkb /Akt/ERK/CREB水平。ANA-12，一种TrkB受体拮抗剂，可以拮抗这些褪黑素的作用，降低褪黑素诱导的神经保护作用。此外，褪黑素挽救了褪黑素受体表达的减少。本研究表明，褪黑激素在缺氧缺血后对视网膜内神经元具有抗凋亡和神经保护作用，至少部分原因是通过调节BDNF-TrkB通路。
Retinopathy of prematurity is a vision-threatening disease associated with retinal hypoxia-ischemia, leading to the death of retinal neurons and chronic neuronal degeneration. During this study, we used the oxygen-induced retinopathy mice model to mimic retinal hypoxia-ischemia phenotypes to investigate further the neuroprotective effect of melatonin on neonatal retinal neurons. Melatonin helped maintain relatively normal inner retinal architecture and thickness and preserve inner retinal neuron populations in avascular areas by rescuing retinal ganglion and bipolar cells, and horizontal and amacrine neurons, from apoptosis. Meanwhile, melatonin recovered visual dysfunction, as reflected by the improved amplitudes and implicit times of a-wave, b-wave, and oscillatory potentials. Additionally, elevated cleaved caspase-3 and Bax protein levels and reduced Bcl-2 protein levels in response to hypoxia-ischemia were diminished after melatonin treatment. Moreover, melatonin increased BDNF and downstream phospho-TrkB/Akt/ERK/CREB levels. ANA-12, a TrkB receptor antagonist, antagonized these melatonin actions and reduced melatonin-induced neuroprotection. Furthermore, melatonin rescued the reduction in melatonin receptor expression. This study suggests that melatonin exerted anti-apoptotic and neuroprotective effects in inner retinal neurons after hypoxia-ischemia, at least partly due to modulation of the BDNF-TrkB pathway.