Rho kinase inhibition: a therapeutic intervention for glaucoma
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After nearly two decades of research on Rho kinase (ROCK) inhibitors for the treatment of ocular hypertension and glaucoma, the FDA approval of Rhopressa® (netarsudil) in 2018 marked the entry of a new class of antiglaucoma drugs in the United States. Netarsudil is both a ROCK inhibitor and a norepinephrine transport (NET) inhibitor. ROCK inhibitors release the cytoskeletal tension by decreasing the actin stress fibers, the extracellular matrix stiffness, and the fibrogenic activation signals. This increases the aqueous humor drainage through the trabecular meshwork and lowers episcleral venous pressure. The NET inhibition decreases the reuptake of norepinephrine and the alpha-adrenergic receptors, thus decreasing inflow by reducing the production of fluid. More recently, the combinatorial IOP-lowering effects have been increased by ROCK inhibitor and prostaglandin drugs, as demonstrated by the approval of Rocklatan® (netarsudil/latanoprost ophthalmic solution). In addition, ROCK inhibitors are also being applied to treat other ocular diseases such as corneal endothelial dysfunction and various forms of diabetic retinopathy. We are midway in the race towards providing a better treatment for ocular hypertension and glaucoma and in an exciting phase of harvesting the fruits of labor. The advent of ROCK inhibitors and the combinatorial drugs for lowering eye pressure is helping glaucoma patients undergo fewer glaucoma surgeries as well as be more compliant with the medications. Further research on drug delivery, compliance, and enhancing the efficacy by lowering the side effects will pave the way for even better treatment options in the future.
Glaucoma Research 2020-2022, pp. 145-172 #14
Edited by: Paul A. Knepper and John R. Samples
© Kugler Publications, Amsterdam, The Netherlands
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