Role of the Rho GTPase/Rho kinase signaling pathway in pathogenesis and treatment of glaucoma: Bench to bedside research.
TLDR
Findings from both basic and clinical studies are summarized that have been instrumental for recognition of the importance of the Rho/Rho kinase signaling pathway in regulation of AH outflow, and in the development of Rho Kinase inhibitors as promising IOP‐ lowering agents for glaucoma treatment.About:
This article is published in Experimental Eye Research.The article was published on 2017-05-01 and is currently open access. It has received 112 citations till now. The article focuses on the topics: Rho-associated protein kinase & Trabecular meshwork.read more
Citations
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Journal ArticleDOI
Two Phase 3 Clinical Trials Comparing the Safety and Efficacy of Netarsudil to Timolol in Patients With Elevated Intraocular Pressure: Rho Kinase Elevated IOP Treatment Trial 1 and 2 (ROCKET-1 and ROCKET-2).
Janet B. Serle,L. Jay Katz,Eugene B McLaurin,Theresa Heah,Nancy Ramirez-Davis,Dale W. Usner,Gary D. Novack,Gary D. Novack,Casey Kopczynski,Rocket Study Groups +9 more
TL;DR: Once-daily dosing of netarsudil 0.02% was found to be effective and well tolerated for the treatment of patients with ocular hypertension and open-angle glaucoma and the novel pharmacology and aqueous humor dynamic effects of this molecule suggest it may be a useful addition to the armamentarium of ocular hypotensive medications.
Journal ArticleDOI
Discovery and Preclinical Development of Netarsudil, a Novel Ocular Hypotensive Agent for the Treatment of Glaucoma
Cheng-Wen Lin,Bryan Sherman,Lori Moore,Carmen L. Laethem,Da-Wen Lu,Padmanabhan P. Pattabiraman,Ponugoti Vasantha Rao,Mitchell A. Delong,Casey Kopczynski +8 more
TL;DR: Netarsudil is a novel ROCK/NET inhibitor with high potency in biochemical and cell-based assays, an ability to produce large and durable IOP reductions in animal models, and favorable pharmacokinetic and ocular tolerability profiles.
Journal ArticleDOI
A multiethnic genome-wide association study of primary open-angle glaucoma identifies novel risk loci.
Hélène Choquet,Seyyedhassan Paylakhi,Stephen C. Kneeland,Khanh K. Thai,Thomas J. Hoffmann,Jie Yin,Mark N. Kvale,Yambazi Banda,Nicholas G. Tolman,Peter A. Williams,Catherine Schaefer,Ronald B. Melles,Neil Risch,Neil Risch,Simon W. M. John,K. Saidas Nair,Eric Jorgenson +16 more
TL;DR: A multiethnic genome-wide association study of POAG in the GERA cohort, which identifies a total of nine novel genetic loci and shows relevant function of FMNL2 and LMX1B using cell line and mouse experiments, provides important insights into glaucoma pathogenesis.
Journal ArticleDOI
Rho kinase inhibitors: a patent review (2014 – 2016)
Olivier Defert,Sandro Boland +1 more
TL;DR: The patents published between September 2013 and September 2016 are reviewed and progress from the compounds series described in the previous review as well as any new expected therapeutic uses for ROCK inhibitors that popped up in the last three years are examined.
Journal ArticleDOI
Long-term Safety and Ocular Hypotensive Efficacy Evaluation of Netarsudil Ophthalmic Solution: Rho Kinase Elevated IOP Treatment Trial (ROCKET-2)
Malik Y. Kahook,Janet B. Serle,Francis S. Mah,Terry Kim,Michael B. Raizman,Theresa Heah,Nancy Ramirez-Davis,Casey Kopczynski,Dale W Usner,Gary D. Novack,Gary D. Novack +10 more
TL;DR: In this randomized, double-masked trial, once-daily dosing of netarsudil 0.02% was effective, consistently lowering IOP through 12 months, and was tolerated by the majority of patients.
References
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The number of people with glaucoma worldwide in 2010 and 2020
Harry A. Quigley,Aimee T. Broman +1 more
TL;DR: Glaucoma is the second leading cause of blindness worldwide, disproportionately affecting women and Asians, and it will be 60.5 million people with OAG and ACG in 2010, increasing to 79.6 million by 2020, and of these, 74% will have OAG.
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Rho GTPases and the Actin Cytoskeleton
TL;DR: Members of the Rho family of small guanosine triphosphatases have emerged as key regulators of the actin cytoskeleton, and through their interaction with multiple target proteins, they ensure coordinated control of other cellular activities such as gene transcription and adhesion.
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Number of people with glaucoma worldwide.
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Rho GTPases in cell biology.
TL;DR: Rho GTPases are molecular switches that control a wide variety of signal transduction pathways in all eukaryotic cells and their ability to influence cell polarity, microtubule dynamics, membrane transport pathways and transcription factor activity is probably just as significant.
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Global prevalence of glaucoma and projections of glaucoma burden through 2040: a systematic review and meta-analysis.
TL;DR: The global prevalence of primary open-angle glaucoma (POAG) and primary angle-closure glauComa (PACG) and the number of affected people in 2020 and 2040 are examined, disproportionally affecting people residing in Asia and Africa.
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