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- Title
Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis.
- Authors
Guorong Li; Chanyoung Lee; Read, A. Thomas; Ke Wang; Ha, Jungmin; Kuhn, Megan; Navarro, Iris; Cui, Jenny; Young, Katherine; Gorijavolu, Rahul; Sulchek, Todd; Kopczynski, Casey; Farsiu, Sina; Samples, John; Challa, Pratap; Ethier, C. Ross; Stamer, W. Daniel
- Abstract
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.
- Subjects
INTRAOCULAR pressure; HOMEOSTASIS; OCULAR hypertension; RHO-associated kinases; LABORATORY mice; HYPERTENSION
- Publication
eLife, 2021, p1
- ISSN
2050-084X
- Publication type
Article
- DOI
10.7554/eLife.60831