文献类型：期刊文献

英文题名：Green-Light-Triggered and Self-Calibrated Cascade Release of Nitric Oxide and Carbon Monoxide for Synergistic Glaucoma Therapy

作者：Chen, Xiaohua[1];Liu, Jiamin[2];Chen, Ming[2];Zhou, Jie[3];Zhang, Yuyang[1];Hu, Xinru[1];Geng, Weixi[1];Mao, Qiyue[4];Kitagishi, Hiroaki[4];Chen, Jinquan[3];Qian, Xuhong[1,5];Yang, Youjun[1];Lei, Yuan[2,6];Luo, Xiao[1,5]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab Chem Biol, Shanghai 200237, Peoples R China;[2]Fudan Univ, Eye Inst, Chinese Acad Med Sci, Shanghai Key Lab Visual Impairment & Restorat,Dept, Shanghai 200031, Peoples R China;[3]East China Normal Univ, State Key Lab Precis Spect, Shanghai 200241, Peoples R China;[4]Doshisha Univ, Fac Sci & Engn, Dept Mol Chem & Biochem, Kyoto 6100321, Japan;[5]East China Normal Univ, Shanghai Engn Res Ctr Mol Therapeut & New Drug Dev, Sch Chem & Mol Engn, Shanghai 200241, Peoples R China;[6]Lanzhou Univ, Inst Occupat Hlth & Environm Hlth, Sch Publ Hlth, Lanzhou 730000, Gansu, Peoples R China

年份：2024

卷号：146

期号：44

起止页码：30361

外文期刊名：JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

收录：;EI(收录号：20244517316920);WOS:【SCI-EXPANDED(收录号:WOS:001338159600001)】；

基金：This work was supported by the National Key Research and Development Program of China (no. 2022YFD1700800), the National Natural Science Foundation of China (nos. 22078098, 22278138, 82070959, and 82271082), the Fundamental Research Funds for the Central Universities (JKY01241620), the Shanghai Academic/Technology Research Leader (22XD1421000), The General Project of Shanghai Natural Science Foundation (21ZR1411500 and 22ZR1409900), the Open Funding Project of the State Key Laboratory of Bioreactor Engineering, the State Key Laboratory of Fine Chemicals (KF2202), and the Medical Engineering Joint Fund of Fudan University (YG202213).

语种：英文

外文关键词：Blood pressure - Brain - Laser beams - Ophthalmology - Pathology

摘要：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.