@article{5e8ba5f269ff4376bb5604bfa1707d38,
title = "Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis",
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.",
author = "Guorong Li and Chanyoung Lee and {Thomas Read}, A. and Ke Wang and Jungmin Ha and Megan Kuhn and Iris Navarro and Jenny Cui and Katherine Young and Rahul Gorijavolu and Todd Sulchek and Casey Kopczynski and Sina Farsiu and John Samples and Pratap Challa and {Ross Ethier}, C. and {Daniel Stamer}, W.",
note = "Funding Information: We thank Ying Hao (Duke Eye Center Core Facility), who prepared histology sections and helped with TEM. Dr. Vibhuti Agrahari helped with the preparation and characterization of the NPs. Dr. Sandra Stinnett performed statistical analysis of data quantifying basement membrane deposits and stiffness measurements. We acknowledge funding support from the BrightFocus Foundation, Clarksburg, MA; Research to Prevent Blindness Foundation, New York; the Georgia Research Alliance, Atlanta, GA; Aerie Pharmaceuticals, Durham, NC; and National Institutes of Health, Washington, DC (EY031710, EY030124, and EY005722). Aerie Pharmaceuticals had input into the choice of several standard endpoint measurements (IOP, outflow facility, smooth muscle actin, and FN expression), but did not have input into other measures, such as TEM (including quantification), OCT imaging and finite element modeling, AFM, and quantification of immunolabeling results. Aerie Pharmaceuticals had no role in the conduct of the research, and other sponsors and funding organizations had no role in either the design or conduct of the research. Publisher Copyright: {\textcopyright} Li et al.",
year = "2021",
month = mar,
doi = "10.7554/eLife.60831",
language = "English (US)",
volume = "10",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications",
}