Glaucoma is a progressive optic neuropathy associated with damage to retinal ganglion cells (RGCs) and disrupted circadian rhythms. Melatonin is a promising substance to ameliorate glaucoma‐associated compromised circadian rhythms, sleep, mood, and retinal cells function. However, studies estimating melatonin effects in glaucoma are currently lacking. Therefore, In this study, we investigated the effect of long‐term (daily at 10:30 pm for 90 days) oral melatonin administration on systemic (Tb) and local to the organ of vision (IOP) circadian rhythms, pattern electroretinogram (PERG), sleep, and mood, depending on glaucoma stage in patients diagnosed with stable or advanced primary open‐angle glaucoma. In a laboratory study in 15 of them, 24‐hour records of salivary melatonin were obtained and MTNR1B receptor gene polymorphism was assessed. Melatonin increased the stability of the Tb circadian rhythm by improving its phase alignment and alignment with IOP. Melatonin time‐dependently decreased IOP and IOP standard deviation (SD). IOP 24‐hour mean and IOP SD decreases were more pronounced in individuals with the higher initial 24‐hour IOP mean. Melatonin improved RGCs function in advanced glaucoma; N95 amplitude increase correlated positively with RGCs loss. The beneficial effects of melatonin on sleep and mood were greater in advanced glaucoma. Finally, delayed salivary melatonin and Tb phases were observed in MTNR1B G‐allele carriers with advanced glaucoma. Combined, these results provide evidence for melatonin efficiency in restoring disrupted circadian rhythms in glaucoma with different effects of melatonin on systemic vs. local circadian rhythms, indicating that a personalized strategy of melatonin administration may further refine its treatment benefits.

中文翻译：

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褪黑激素减轻昼夜节律紊乱，降低眼内压，并改善青光眼中视网膜神经节细胞的功能

青光眼是一种进行性视神经病变，与视网膜神经节细胞 (RGC) 损伤和昼夜节律紊乱有关。褪黑激素是一种很有前途的物质，可以改善青光眼相关的昼夜节律、睡眠、情绪和视网膜细胞功能。然而，目前缺乏估计褪黑激素对青光眼影响的研究。因此，在这项研究中，我们研究了在10:30长期（每日效果 PM90 天）口服褪黑激素对全身 (Tb) 和局部视觉器官 (IOP) 昼夜节律、模式视网膜电图 (PERG)、睡眠和情绪，取决于诊断为稳定或晚期原发性开放性青光眼的患者的青光眼分期角型青光眼。在其中 15 人的实验室研究中，获得了唾液褪黑激素的 24 小时记录，并评估了 MTNR1B 受体基因多态性。褪黑激素通过改善其相位对齐和与 IOP 的对齐来增加 Tb 昼夜节律的稳定性。褪黑激素时间依赖性降低 IOP 和 IOP 标准偏差 (SD)。IOP 24 小时平均值和 IOP SD 降低在初始 24 小时 IOP 平均值较高的个体中更为明显。褪黑激素改善晚期青光眼的 RGC 功能；N95 振幅增加与 RGC 损失呈正相关。褪黑激素对晚期青光眼的睡眠和情绪的有益影响更大。最后，在患有晚期青光眼的 MTNR1B G 等位基因携带者中观察到延迟的唾液褪黑激素和 Tb 阶段。结合起来，这些结果提供了褪黑激素在恢复青光眼中断的昼夜节律方面的效率的证据，褪黑激素对全身和局部昼夜节律的影响不同，表明褪黑激素的个性化给药策略可能会进一步完善其治疗益处。