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Abstract #126800 Published in IGR 25-2
A Light-Activatable Nitric Oxide Donor for Targeted Glaucoma Therapy with Real-Time Monitoring Capabilities
Liu J; Lu Y; Tian Y; Liu Q; Sun X; Liu Y; Lei YAdvanced healthcare materials 2025; 14: e2404221
Primary open-angle glaucoma (POAG), the most common form of glaucoma, is characterized by a gradual increase in intraocular pressure (IOP). Nitric oxide (NO) donors are promising treatments for POAG, but their effectiveness requires selective NO release triggered by ocular-relevant stimuli. RhNO-Ab, a visible light-activatable NO donor and fluorescent probe is introduced. RhNO-Ab releases NO from its N-nitroso group and transforms from a non-fluorescent 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-Ab with ABCA1 antibody modification. Administration of RhNO-Ab with light at 30, 20, and 10 µm significantly reduces IOP in NOS3 KO mice by 2.11 mmHg (12.50%, n = 6), 1.77 mmHg (9.88%, n = 6), and 1.55 mmHg (8.23%, n = 6) 3 h post-treatment (p < 0.05). RhNO-Ab with light also reduces transendothelial electrical resistance (TEER) in Schlemm's canal (SC) endothelial cells (n = 3, p < 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-Ab offers visible light-triggered therapeutic NO release and real-time monitoring, making it a promising novel strategy for POAG treatment.
Eye Institute and Department of Ophthalmology, Eye & 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.
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