Xiaohua Chen, Jiamin Liu, Ming Chen, Jie Zhou, Yuyang Zhang, Xinru Hu, Weixi Geng, Qiyue Mao, Hiroaki Kitagishi, Jinquan Chen, Xuhong Qian, Youjun Yang, Yuan Lei, Xiao Luo
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This leads to the concept of “gas waltz therapy” for glaucoma, in which NO is released to reduce IOP and stoichiometric CO is coreleased to suppress oxidative stress. <b>CND570</b> is the first phototriggered cascade NO/CO donor, to the best of our knowledge. Notably, the release of NO/CO is accompanied by the concomitant release of a rhodamine dye whose bright fluorescence is harnessed as a convenient calibration mechanism of the gas release profile. <b>CND570</b> exhibits excellent transcorneal permeability and reaches the target aqueous humor outflow pathway. Further, green-light irradiation triggers release of CO and NO in the eye tissue of glaucoma mice. NO and CO could promote the upregulation of soluble guanylate cyclase (sGC) in both <i>in vitro</i> and <i>in vivo</i> models. Notably, <b>CND570</b> treatment significantly reduces the oxidative stress associated with glaucoma. 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Notably, the release of NO/CO is accompanied by the concomitant release of a rhodamine dye whose bright fluorescence is harnessed as a convenient calibration mechanism of the gas release profile. <b>CND570</b> exhibits excellent transcorneal permeability and reaches the target aqueous humor outflow pathway. Further, green-light irradiation triggers release of CO and NO in the eye tissue of glaucoma mice. NO and CO could promote the upregulation of soluble guanylate cyclase (sGC) in both <i>in vitro</i> and <i>in vivo</i> models. Notably, <b>CND570</b> treatment significantly reduces the oxidative stress associated with glaucoma. 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引用次数: 0
摘要
青光眼是一种视神经退行性病变,由氧化应激和机械应激的恶性循环驱动。目前的临床治疗主要是通过降低眼压来减轻机械应激。由于氧化应激未得到重视,机械应激的复发和恶化不可避免。一氧化氮(NO)和一氧化碳(CO)分别是扩张血管和抗炎的内源性气体信号分子。越来越多的证据表明,一氧化氮和一氧化碳之间存在着错综复杂的相互作用,就像跳华尔兹需要两个人才能完成一样。这就产生了治疗青光眼的 "气体华尔兹疗法 "的概念,即释放 NO 以降低眼压,同时释放等量 CO 以抑制氧化应激。据我们所知,CND570 是首个光触发级联 NO/CO 供体。值得注意的是,NO/CO 的释放伴随着罗丹明染料的同时释放,其明亮的荧光被用作气体释放曲线的便捷校准机制。CND570 具有极佳的跨角膜渗透性,可到达目标水房水流出途径。此外,绿光照射可诱发青光眼小鼠眼组织中 CO 和 NO 的释放。在体外和体内模型中,NO和CO都能促进可溶性鸟苷酸环化酶(sGC)的上调。值得注意的是,CND570 能显著降低与青光眼相关的氧化应激。基于 NO/CO 的气体华尔兹疗法是治疗青光眼的一种前景广阔的新途径。
Green-Light-Triggered and Self-Calibrated Cascade Release of Nitric Oxide and Carbon Monoxide for Synergistic Glaucoma Therapy
Glaucoma is an optic degenerative neuropathy that is driven by a vicious cycle of oxidative stress and mechanical stress. Current clinical treatments aim exclusively at alleviating mechanical stress by reducing the intraocular pressure (IOP). With the unattended oxidative stress, recurrence and deterioration of mechanical stress are inevitable. Nitric oxide (NO) and carbon monoxide (CO) are endogenous gaseous signaling molecules for vasodilation and anti-inflammation, respectively. Mounting evidence suggests an intricate interplay between NO and CO to mediate their biological roles, like how it takes two to dance a waltz. This leads to the concept of “gas waltz therapy” for glaucoma, in which NO is released to reduce IOP and stoichiometric CO is coreleased to suppress oxidative stress. CND570 is the first phototriggered cascade NO/CO donor, to the best of our knowledge. Notably, the release of NO/CO is accompanied by the concomitant release of a rhodamine dye whose bright fluorescence is harnessed as a convenient calibration mechanism of the gas release profile. CND570 exhibits excellent transcorneal permeability and reaches the target aqueous humor outflow pathway. Further, green-light irradiation triggers release of CO and NO in the eye tissue of glaucoma mice. NO and CO could promote the upregulation of soluble guanylate cyclase (sGC) in both in vitro and in vivo models. Notably, CND570 treatment significantly reduces the oxidative stress associated with glaucoma. NO/CO-based gas waltz therapy is a promising new avenue for glaucoma treatment.
期刊介绍:
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