Potential of melatonin to treat or prevent age-related macular degeneration through stimulation of telomerase activity
Potential of melatonin to treat or prevent age-related macular degeneration through stimulation of telomerase activity
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DOI：
10.1016/j.mehy.2010.08.036
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发表时间：
2011-01-01
影响因子：
4.7
通讯作者：
Rastmanesh, Reza
中科院分区：
文献类型：
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作者：
Rastmanesh, Reza
褪黑激素可能在年龄相关性黄斑变性（AMD）的发生中发挥因果作用。视网膜色素上皮 (RPE) 的复制能力和对损伤的反应在衰老过程中会受到损害。通过抗氧化剂预防端粒缩短可能是减少 RPE 细胞氧化应激累积效应的有效方法。褪黑素是一种众所周知的抗氧化剂，其作为两亲剂的作用有利，可能比常用的亲脂性或亲水性抗氧化剂更有益于 AMD 患者。它还可能通过抗氧化机制以外的机制发挥作用，因为褪黑激素具有位于 RPE 中的受体，其局部充当神经激素和/或神经调节剂。一项临床试验结果表明，AMD 患者每晚睡前口服 3 毫克褪黑激素，持续 3 个月，可减少病理性黄斑变化。我推测褪黑激素通过下调 hTERT（端粒酶催化亚基）的表达并刺激 RPE 中的端粒酶活性来发挥额外的作用，从而有助于预防或治疗 AMD。我建议将褪黑激素作为药物和/或富含褪黑激素的食物进行治疗，特别是对于血清褪黑激素水平较低的 AMD 患者或高危患者，可能是预防和/或治疗 AMD 的另一种方法。我认为褪黑素有可能预防 RPE 端粒缩短，同时不排除其他机制，即抗氧化特性和/或恢复内部血视网膜屏障 (iBRB) 完整性、降低血管内皮生长因子 (VEGF) 和一氧化氮 (NO) 水平以及辣根过氧化物酶 (HRP) 泄漏、抑制缺氧诱导因子 1α (H1F-1α) 在缺氧条件下的稳定性。 (C) 2010 Elsevier Ltd. 保留所有权利。
Melatonin may play a causal role in the occurrence of age-related macular degeneration (AMD). Replicative capacity and response to injury in the retinal pigment epithelium (RPE) is compromised during aging. Prevention of telomere shortening by antioxidants may be a useful approach for reducing the cumulative effects of oxidative stress in RPE cells. Melatonin, a well known antioxidant, which acts advantageously as an amphiphilic agent, may benefit AMD patients more than commonly used lipophilic or hydrophilic antioxidants. It also may act through mechanisms other than antioxidant mechanisms because melatonin has receptors localized in the RPE, which act locally as a neurohormone and/or neuromodulator. Results of a clinical trial showed that 3 mg melatonin given orally each night at bedtime for 3 months to AMD patients reduced pathologic macular changes. I hypothesize that melatonin exerts additional benefit through down-regulating hTERT (catalytic subunit if telomerase) expression and stimulated telomerase activity in RPE, which subsequently helps to prevent or treat AMD. I suggest that melatonin therapy as pharmacologic agents and/or melatonin-rich foods, especially in AMD patients with measured low serum melatonin levels or high risk patients would be possibly an alternative approach to prevent and/or treat AMD. I suggest that melatonin has potential to prevent telomere shortening in RPE, while not precluding other mechanisms, namely antioxidative properties and/or restoration of inner blood-retina barrier (iBRB) integrity, reduced vascular endothelial growth factor (VEGF) and nitric oxide (NO) levels as well as leakage of horseradish peroxidase (HRP), inhibiting hypoxia-inducible factor-1alpha (H1F-1alpha) stabilization under hypoxia. (C) 2010 Elsevier Ltd. All rights reserved.