Related Experiment Video
Updated: Jun 16, 2025

Full-Circle Cauterization of Limbal Vascular Plexus for Surgically Induced Glaucoma in Rodents
Published on: February 15, 2022
Development of Nitric Oxide-Donating Netarsudil Derivatives as a Synergistic Therapy for Glaucoma with Reduced Ocular
Cunrui Li1, Mingchao Zhu1, Songqi Liu1
1State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 211198, China.
Abstract:
Based on the synergistic therapeutic effect of nitric oxide (NO) and Rho-associated protein kinase (ROCK) inhibitors on glaucoma, a series of NO-donating Netarsudil derivatives were designed, synthesized, and their activities in vitro and in vivo were evaluated. Among them, (S)-10e released an appropriate amount of NO in aqueous humor in vitro and displayed potent ROCK inhibition. Topical administration of (S)-10e significantly lowered intraocular pressure in an acute ocular hypertension rabbit model and protected retinal ganglion cells in a magnetic microbead occlusion mouse model. A metabolism investigation revealed that (S)-10e released 7a, a metabolite after NO releasing, and 13, an active metabolite of (S)-Netarsudil, in rabbit eyes. Notably, introducing an NO donor moiety attenuated ROCK inhibition-induced ocular irritation in an sGC-independent manner, suggesting that the attenuated conjunctival hyperemia effect of (S)-10e is related to the NO-induced protein S-nitrosation of phosphodiesterase 3A (PDE3A). Overall, (S)-10e is a promising candidate for glaucoma treatment.
Related Concept Videos
Open Angle Glaucoma: Treatment
Drugs such as carbonic anhydrase inhibitors, α2- and...
Antihypertensive Drugs: Vasodilators
Nitric Oxide Signaling Pathway
Angle Closure Glaucoma: Treatment
Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
Antianginal Drugs: Nitrates and β-Blockers
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow....

