RT Journal Article
SR Electronic
T1 Antifibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.17.208207
DO 10.1101/2020.07.17.208207
A1 Guorong Li
A1 Chanyoung Lee
A1 A. Thomas Read
A1 Ke Wang
A1 Iris Navarro
A1 Jenny Cui
A1 Katherine M. Young
A1 Rahul Gorijavolu
A1 Todd Sulchek
A1 Casey C. Kopczynski
A1 Sina Farsiu
A1 John R. Samples
A1 Pratap Challa
A1 C. Ross Ethier
A1 W. Daniel Stamer
YR 2020
UL http://biorxiv.org/content/early/2020/07/17/2020.07.17.208207.abstract
AB 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, 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.