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.

中文翻译：

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褪黑激素对缺氧缺血后新生小鼠视网膜内神经元的保护作用

早产儿视网膜病变是一种威胁视力的疾病，与视网膜缺氧缺血相关，可导致视网膜神经元死亡和慢性神经元变性。在这项研究中，我们使用氧诱导的视网膜病变小鼠模型来模拟视网膜缺氧缺血表型，以进一步研究褪黑激素对新生儿视网膜神经元的神经保护作用。褪黑激素通过从细胞凋亡中拯救视网膜神经节和双极细胞以及水平和无长突神经元，帮助维持相对正常的内部视网膜结构和厚度，并保护无血管区域的内部视网膜神经元群。同时，褪黑激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，褪黑激素治疗后，由于缺氧缺血引起的裂解 caspase-3 和 Bax 蛋白水平升高以及 Bcl-2 蛋白水平降低。此外，褪黑激素增加了 BDNF 和下游磷酸化-TrkB/Akt/ERK/CREB ​​水平。ANA-12 是一种 TrkB 受体拮抗剂，可拮抗这些褪黑激素的作用并降低褪黑激素诱导的神经保护作用。此外，褪黑激素挽救了褪黑激素受体表达的减少。这项研究表明，褪黑激素在缺氧缺血后对内部视网膜神经元发挥抗凋亡和神经保护作用，至少部分是由于 BDNF-TrkB 通路的调节。拮抗这些褪黑激素作用并降低褪黑激素诱导的神经保护作用。此外，褪黑激素挽救了褪黑激素受体表达的减少。这项研究表明，褪黑激素在缺氧缺血后对内部视网膜神经元发挥抗凋亡和神经保护作用，至少部分是由于 BDNF-TrkB 通路的调节。拮抗这些褪黑激素作用并降低褪黑激素诱导的神经保护作用。此外，褪黑激素挽救了褪黑激素受体表达的减少。这项研究表明，褪黑激素在缺氧缺血后对内部视网膜神经元发挥抗凋亡和神经保护作用，至少部分是由于 BDNF-TrkB 通路的调节。