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Nitric oxide (NO) donors are promising treatments for POAG, but their effectiveness requires selective NO release triggered by ocular\u2010relevant stimuli. RhNO\u2010Ab, a visible light\u2010activatable NO donor and fluorescent probe is introduced. RhNO\u2010Ab releases NO from its N\u2010nitroso group and transforms from a non\u2010fluorescent spirolactone to fluorescent Rhodamine (Rh) upon NO release. In vitro studies, including in bulk and single molecule level demonstrated a rapid NO release and fluorescence recovery upon light irradiation. Immunofluorescence shows enhanced delivery to target tissues of RhNO\u2010Ab with ABCA1 antibody modification. Administration of RhNO\u2010Ab with light at 30, 20, and 10\u00a0\u00b5<jats:sc>m<\/jats:sc> significantly reduces IOP in NOS3 KO mice by 2.11\u00a0mmHg (12.50%, n = 6), 1.77\u00a0mmHg (9.88%, n = 6), and 1.55\u00a0mmHg (8.23%, n = 6) 3\u00a0h post\u2010treatment (<jats:sup>*<\/jats:sup><jats:italic>p<\/jats:italic> &lt; 0.05). RhNO\u2010Ab with light also reduces transendothelial electrical resistance (TEER) in Schlemm's canal (SC) endothelial cells (n = 3, <jats:sup>*<\/jats:sup><jats:italic>p<\/jats:italic> &lt; 0.05) and upregulates soluble guanylate cyclase (sGC) mRNA and protein expression in mouse outflow tissues and human trabecular meshwork (HTM) cells. Unlike traditional NO donors, RhNO\u2010Ab offers visible light\u2010triggered therapeutic NO release and real\u2010time monitoring, making it a promising novel strategy for POAG treatment.<\/jats:p>","DOI":"10.1002\/adhm.202404221","type":"journal-article","created":{"date-parts":[[2025,3,19]],"date-time":"2025-03-19T03:59:51Z","timestamp":1742356791000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Light\u2010Activatable Nitric Oxide Donor for Targeted Glaucoma Therapy with Real\u2010Time Monitoring Capabilities"],"prefix":"10.1002","volume":"14","author":[{"given":"Jiamin","family":"Liu","sequence":"first","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye &amp; ENT Hospital Fudan University NHC Key Laboratory of Myopia and Related Eye Diseases Key Laboratory of Myopia and Related Eye Diseases Chinese Academy of Medical Sciences Shanghai Key Laboratory of Visual Impairment and Restoration  Shanghai 200031 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yankun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering School of Engineering China Pharmaceutical University  Nanjing 211198 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Tian","sequence":"additional","affiliation":[{"name":"Eye Institute and Department of Ophthalmology Eye &amp; 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