Department of Biochemistry and Molecular Biology, Faculty of Optics and Optometry, Universidad Complutense de Madrid, Madrid, Spain.
Department of Ophthalmology, OPHTHALMEDIC and I.P.O. Institute of Ophthalmology, Balearic Island, Spain.
Exp Eye Res. 2022 Feb;215:108912. doi: 10.1016/j.exer.2021.108912. Epub 2021 Dec 26.
Oxidative stress, generated because of an imbalance between reactive oxygen species (ROS) generation and elimination, is associated with lens damage and cataract progression. ROS generation is known to activate NLRP3 (nucleotide-binding oligomerization domain-like receptor family, pyrin domain-cointaining 3) inflammasome, and is believed to be an important link between oxidative stress and inflammation, that is also related to cataract development. Potential oxidative hazard to the lens by white light-emitting diode (LED) light, a source of illumination commonly used nowadays, has been suggested, although available information is limited. In this work, we evaluated the cytotoxicity induced by hydrogen peroxide (an oxidative stressor agent) and white LED light in lens epithelial cells as well as melatonin ability to counteract the effects induced by them. Melatonin is a neurohormone secreted by different ocular structures that could be useful to alleviate oxidative damage induced by different oxidative stressors in lens. Particularly, the modulation of Nrf2 (nuclear erythroid 2-related factor)/Keap 1 (Kelch-like ECH-associated protein 1), an essential oxidative stress regulator, and NLRP3 activity by melatonin was evaluated in lens epithelial cells. ROS levels rose after white LED light exposure and cell viability was reduced after challenge with oxidative stressor agents. Melatonin prevented cell death triggered by hydrogen peroxide and white LED light, precluded ROS generation induced by white LED light and promoted antioxidant lens capacity through upregulation of Nrf2 protein levels and SOD activity. NLRP3, caspase-1 and IL1-β expression significantly increased in human lens cells exposed to HO or irradiated with white LED light. Activation of NLRP3 inflammasome triggered by oxidative stressors was also abrogated by melatonin. Attenuation of inflammatory and cytotoxic effects induced by oxidative stressors provided by melatonin in lens indicate the interest of this molecule as a potential therapeutic agent for cataract prevention/management.
氧化应激是由于活性氧（ROS）的产生和消除之间的失衡而产生的，与晶状体损伤和白内障进展有关。ROS 的产生已知会激活 NLRP3（核苷酸结合寡聚化结构域样受体家族，富含吡喃结构域 3）炎症小体，并且被认为是氧化应激和炎症之间的重要联系，这也与白内障的发展有关。虽然目前可用的信息有限，但已经有人提出，白光发光二极管（LED）灯作为当今常用的照明光源，可能会对晶状体造成潜在的氧化危害。在这项工作中，我们评估了过氧化氢（一种氧化应激剂）和白色 LED 光对晶状体上皮细胞的细胞毒性，以及褪黑素抵抗它们诱导的作用的能力。褪黑素是一种由不同眼结构分泌的神经激素，可能有助于减轻晶状体中不同氧化应激源引起的氧化损伤。特别是，评估了褪黑素对晶状体上皮细胞中 Nrf2（核红细胞 2 相关因子）/Keap1（Kelch 样 ECH 相关蛋白 1）的调节作用，Nrf2/Keap1 是一种重要的氧化应激调节剂，以及 NLRP3 活性。暴露于白色 LED 光后，ROS 水平升高，氧化应激剂处理后细胞活力降低。褪黑素可预防过氧化氢和白色 LED 光引起的细胞死亡，防止白色 LED 光诱导的 ROS 生成，并通过上调 Nrf2 蛋白水平和 SOD 活性促进抗氧化晶状体能力。在暴露于 HO 或用白色 LED 光照射的人晶状体细胞中，NLRP3、caspase-1 和 IL1-β 的表达显著增加。氧化应激剂激活 NLRP3 炎症小体也被褪黑素阻断。褪黑素减轻晶状体中氧化应激剂引起的炎症和细胞毒性作用，表明该分子作为预防/管理白内障的潜在治疗剂的兴趣。
