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Rho kinase inhibitors getting to the heart of the matter

  • Lynda Charters
April 30, 2019
  • Glaucoma

Abstract / Synopsis: 

Glaucoma drug therapy continues to evolve with Rho kinase inhibitors that specifically target glaucomatous abnormalities such as trabecular meshwork outflow.

Rho kinase inhibitors—the newest drugs introduced for treating glaucoma—"get to the heart of the matter” by targeting specific glaucomatous abnormalities, such as trabecular meshwork outflow, said Yvonne Ou, MD.

Previously released glaucoma drugs have instead lowered IOP by increasing uveoscleral outflow or decreasing the production of aqueous humor.

Rho kinases, ROCK 1 and 2, are present throughout the body as well as in the trabecular meshwork, and they are instrumental in actomyosin contractility.

Overall, they increase cellular stiffness by modulating microtubules, actin filament disassembly, and forming focal adhesion complexes, said Dr. Ou, associate professor of ophthalmology, and co-director of the glaucoma service, University of California, San Francisco.

Dr. Ou’s mentor—David Epstein, MD, whom she credits with ground-breaking insights into treatments for glaucoma—challenged ophthalmic researchers to remain focused on the main goal in glaucoma research, i.e., new treatments must focus on the diseased trabecular meshwork and be specific to the optic nerve in order to address the basic abnormalities in primary open-angle glaucoma.

He emphasized that none of the treatments available at the time of his comments addressed glaucomatous abnormalities.

Dr. Epstein’s subsequent research and his collaboration with cell biologists and with Paul Kaufman, MD, and Vasantha Rao, PhD, made discoveries that led to the development of Rho kinase inhibitors as an outflow drug, which acts directly on the trabecular meshwork.

Rho kinase inhibitors answered Dr. Epstein’s challenge in that they focus on a glaucomatous abnormality.

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Disclosures: 

Yvonne Ou, MD
E: [email protected]
Dr. Ou is a consultant and advisor to Merck & Co. Inc.

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