Effects of Rho Kinase Inhibitors on Intraocular Pressure and Aqueous Humor Dynamics in Nonhuman Primates and Rabbits

2016 ◽  
Vol 32 (6) ◽  
pp. 355-364 ◽  
Author(s):  
Carol B. Toris ◽  
Marsha A. McLaughlin ◽  
Douglas P. Dworak ◽  
Shan Fan ◽  
Shane Havens ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Aqueous Humor ◽  
Nonhuman Primates ◽  
Kinase Inhibitors ◽  
Rho Kinase ◽  
Aqueous Humor Dynamics ◽  
Rho Kinase Inhibitors

scholarly journals Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Guorong Li ◽  
Chanyoung Lee ◽  
A Thomas Read ◽  
Ke Wang ◽  
Jungmin Ha ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Ocular Hypertension ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Prospective Clinical Study ◽  
Rho Kinase Inhibitors ◽  
Rho Kinase Inhibitor ◽  
Intraocular Pressure Elevation ◽  
Outflow Pathway

Glucocorticoids are widely used as an ophthalmic medication. A common, sight-threatening adverse event of glucocorticoid usage is ocular hypertension, caused by dysfunction of the conventional outflow pathway. We report that netarsudil, a rho-kinase inhibitor, decreased glucocorticoid-induced ocular hypertension in patients whose intraocular pressures were poorly controlled by standard medications. Mechanistic studies in our established mouse model of glucocorticoid-induced ocular hypertension show that netarsudil both prevented and reduced intraocular pressure elevation. Further, netarsudil attenuated characteristic steroid-induced pathologies as assessed by quantification of outflow function and tissue stiffness, and morphological and immunohistochemical indicators of tissue fibrosis. Thus, rho-kinase inhibitors act directly on conventional outflow cells to prevent or attenuate fibrotic disease processes in glucocorticoid-induced ocular hypertension in an immune-privileged environment. Moreover, these data motivate the need for a randomized prospective clinical study to determine whether netarsudil is indeed superior to first-line anti-glaucoma drugs in lowering steroid-induced ocular hypertension.

scholarly journals Antifibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis

2020 ◽  
Author(s):  
Guorong Li ◽  
Chanyoung Lee ◽  
A. Thomas Read ◽  
Ke Wang ◽  
Iris Navarro ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Ocular Hypertension ◽  
Kinase Inhibitors ◽  
Kinase Inhibitor ◽  
Rho Kinase ◽  
Tissue Stiffness ◽  
Rho Kinase Inhibitors ◽  
Rho Kinase Inhibitor ◽  
Intraocular Pressure Elevation ◽  
Outflow Pathway

AbstractGlucocorticoids are widely used as an ophthalmic medication. A common, sight-threatening adverse event of glucocorticoid usage is ocular hypertension, caused by dysfunction of the conventional outflow pathway. We report that netarsudil, a rho-kinase inhibitor, rapidly reversed glucocorticoid-induced ocular hypertension in patients whose intraocular pressures were uncontrolled by standard medications. Mechanistic studies in our established mouse model of glucocorticoid-induced ocular hypertension show that netarsudil both prevented and reversed intraocular pressure elevation. Further, netarsudil reversed characteristic steroid-induced pathologies as assessed by quantification of outflow function and tissue stiffness, and morphological and immunohistochemical indicators of tissue fibrosis. Thus, rho-kinase inhibitors act directly on conventional outflow cells to efficaciously prevent or reverse fibrotic disease processes in glucocorticoid-induced ocular hypertension. These data motivate a novel indication for these agents to prevent or treat ocular hypertension secondary to glucocorticoid administration, and demonstrate the antifibrotic effects of rho-kinase inhibitors in an immune-privileged environment.

Probing Cellular Outcomes Using Heterobivalent Constructs

2019 ◽  
Author(s):  
Rohit Bhadoria ◽  
Kefeng Ping ◽  
Christer Lohk ◽  
Ivar Järving ◽  
Pavel Starkov
Keyword(s):  
Cell Viability ◽  
Small Molecules ◽  
Cellular Uptake ◽  
Kinase Inhibitors ◽  
Rho Kinase ◽  
Intracellular Delivery ◽  
Rho Kinase Inhibitors

<div> <div> <div> <p>Conjugation techniques are central to improving intracellular delivery of bioactive small molecules. However, tracking and assessing the overall biological outcome of these constructs remains poorly understood. We addressed this issue by having developed a focused library of heterobivalent constructs based on Rho kinase inhibitors to probe various scenarios. By comparing induction of a phenotype of interest vs. cell viability vs. cellular uptake, we demonstrate that such conjugates indeed lead to divergent cellular outcomes. </p> </div> </div> </div>

scholarly journals Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

2021 ◽  
Vol 22 (3) ◽  
pp. 1170
Author(s):  
Arunbalaji Pugazhendhi ◽  
Margaret Hubbell ◽  
Pooja Jairam ◽  
Balamurali Ambati
Keyword(s):  
Risk Factors ◽  
Macular Degeneration ◽  
Kinase Inhibitors ◽  
Rho Kinase ◽  
The Elderly ◽  
Age Related Macular Degeneration ◽  
Gene Therapies ◽  
Rho Kinase Inhibitors ◽  
Age Related ◽  
Endothelial Growth Factor

Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. Risk factors such as age, race, genetics, iris color, smoking, drinking, BMI, and diet all play a part in nvAMD’s progression, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the mainstay of treatment. Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. Newer therapies such as gene therapies, Rho-kinase inhibitors, and levodopa offer potential new targets for treatment.

scholarly journals Towards axonal regeneration and neuroprotection in glaucoma: Rho kinase inhibitors as promising therapeutics

2015 ◽  
Vol 131 ◽  
pp. 105-119 ◽  
Author(s):  
Sarah Van de Velde ◽  
Lies De Groef ◽  
Ingeborg Stalmans ◽  
Lieve Moons ◽  
Inge Van Hove
Keyword(s):  
Axonal Regeneration ◽  
Kinase Inhibitors ◽  
Rho Kinase ◽  
Rho Kinase Inhibitors

scholarly journals Fragment-Based and Structure-Guided Discovery and Optimization of Rho Kinase Inhibitors

2012 ◽  
Vol 55 (5) ◽  
pp. 2474-2478 ◽  
Author(s):  
Rongshi Li ◽  
Mathew P. Martin ◽  
Yan Liu ◽  
Binglin Wang ◽  
Ronil A. Patel ◽  
...  
Keyword(s):  
Kinase Inhibitors ◽  
Rho Kinase ◽  
Guided Discovery ◽  
Rho Kinase Inhibitors
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