Department of Ophthalmology, Key Laboratory of Vision Loss and Restoration, Ministry of Education, Peking University Third Hospital, Beijing, China.
National Engineering Laboratory for Animal Breeding, Key Laboratory of Animal Genetics, Breeding and Reproduction of the Ministry of Agriculture, College of Animal Science and Technology, China Agricultural University, Beijing, China.
J Pineal Res. 2017 Oct;63(3). doi: 10.1111/jpi.12428. Epub 2017 Jun 20.
Retinitis pigmentosa (RP) comprises a group of incurable inherited retinal degenerations. Targeting common processes, instead of mutation-specific treatment, has proven to be an innovative strategy to combat debilitating retinal degeneration. Growing evidence indicates that melatonin possesses a potent activity against neurodegenerative disorders by mitigating cell damage associated with apoptosis and inflammation. Given the pleiotropic role of melatonin in central nervous system, the aim of the present study was to investigate whether melatonin would afford protection against retinal degeneration in autosomal recessive RP (arRP). Rd10, a well-characterized murine model of human arRP, received daily intraperitoneal injection of melatonin (15 mg/kg) between postnatal day (P) 13 and P30. Retinas treated with melatonin or vehicle were harvested for analysis at P30 and P45, respectively. The findings showed that melatonin could dampen the photoreceptors death and delay consequent retinal degeneration. We also observed that melatonin weakened the expression of glial fibrillary acidic protein (GFAP) in Müller cells. Additionally, melatonin could alleviate retinal inflammatory response visualized by IBA1 staining, which was further corroborated by downregulation of inflammation-related genes, such as tumor necrosis factor alpha (Tnf-α), chemokine (C-C motif) ligand 2 (Ccl2), and chemokine (C-X-C motif) ligand 10 (Cxcl10). These data revealed that melatonin could ameliorate retinal degeneration through potentially attenuating apoptosis, reactive gliosis, and microglial activation in rd10 mice. Moreover, these results suggest melatonin as a promising agent improving photoreceptors survival in human RP.
色素性视网膜炎（RP）是一组不可治愈的遗传性视网膜变性。针对共同的过程，而不是针对突变的特异性治疗，已被证明是对抗衰弱性视网膜变性的一种创新策略。越来越多的证据表明，褪黑素通过减轻与细胞凋亡和炎症相关的细胞损伤，具有对抗神经退行性疾病的强大活性。鉴于褪黑素在中枢神经系统中的多效性作用，本研究旨在探讨褪黑素是否能为常染色体隐性 RP（arRP）提供对视网膜变性的保护。Rd10 是一种经过充分研究的人类 arRP 小鼠模型，在出生后第 13 天（P13）至 P30 期间每天接受腹腔内注射褪黑素（15mg/kg）。用褪黑素或载体处理的视网膜分别在 P30 和 P45 时收获用于分析。研究结果表明，褪黑素可以抑制感光细胞的死亡并延缓随后的视网膜变性。我们还观察到，褪黑素减弱了 Müller 细胞中胶质纤维酸性蛋白（GFAP）的表达。此外，褪黑素可以减轻 IBA1 染色可视化的视网膜炎症反应，这进一步得到炎症相关基因下调的证实，如肿瘤坏死因子-α（Tnf-α）、趋化因子（C-C 基元）配体 2（Ccl2）和趋化因子（C-X-C 基元）配体 10（Cxcl10）。这些数据表明，褪黑素可以通过潜在地减轻 rd10 小鼠中的细胞凋亡、反应性神经胶质增生和小胶质细胞激活来改善视网膜变性。此外，这些结果表明褪黑素作为一种有前途的药物，可以改善人类 RP 中的感光细胞存活。
