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.

中文翻译：

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褪黑素延缓常染色体隐性遗传性视网膜色素变性的小鼠模型中的感光细胞变性

色素性视网膜炎（RP）包括一组无法治愈的遗传性视网膜变性。事实证明，针对通用过程而不是针对突变的治疗是对抗衰弱性视网膜变性的创新策略。越来越多的证据表明，褪黑激素通过减轻与凋亡和炎症相关的细胞损伤，具有有效的抗神经退行性疾病的活性。考虑到褪黑激素在中枢神经系统中的多效性作用，本研究的目的是研究褪黑激素是否能在常染色体隐性RP（arRP）中提供抗视网膜变性的保护作用。10路，是一个很好的人arRP鼠模型，在出生后第13天至第30天之间每天接受腹膜内注射褪黑激素（15 mg / kg）。分别在P30和P45收获用褪黑激素或媒介物处理过的视网膜进行分析。这些发现表明褪黑激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细胞中神经胶质纤维酸性蛋白（GFAP）的表达。此外，褪黑激素可以减轻通过IBA1染色可见的视网膜炎症反应，炎症相关基因的下调进一步证实了这种炎症反应，例如肿瘤坏死因子α（Tnf‐ α），趋化因子（CC母题）配体2（Ccl2）和趋化因子（C‐X‐C基序）配体10（Cxcl10）。这些数据表明，褪黑激素可以通过潜在地减弱rd10小鼠的细胞凋亡，反应性神经胶质细胞增生和小胶质细胞活化来改善视网膜变性。此外，这些结果表明褪黑激素是改善人RP中光感受器存活的有前途的药物。