Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

Antifibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis

Guorong Li, Chanyoung Lee, A. Thomas Read, Ke Wang, Iris Navarro, Jenny Cui, Katherine M. Young, Rahul Gorijavolu, Todd Sulchek, View ORCID ProfileCasey C. Kopczynski, Sina Farsiu, John R. Samples, Pratap Challa, C. Ross Ethier, View ORCID ProfileW. Daniel Stamer
doi: https://doi.org/10.1101/2020.07.17.208207
Guorong Li
1Department of Ophthalmology, Duke University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Chanyoung Lee
2Department of Biomedical Engineering, Georgia Institute of Technology/Emory University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
A. Thomas Read
2Department of Biomedical Engineering, Georgia Institute of Technology/Emory University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Ke Wang
2Department of Biomedical Engineering, Georgia Institute of Technology/Emory University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Iris Navarro
1Department of Ophthalmology, Duke University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jenny Cui
1Department of Ophthalmology, Duke University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Katherine M. Young
2Department of Biomedical Engineering, Georgia Institute of Technology/Emory University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Rahul Gorijavolu
1Department of Ophthalmology, Duke University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Todd Sulchek
3Department of Mechanical Engineering, Georgia Institute of Technology
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Casey C. Kopczynski
4Aerie Pharmaceuticals, Inc., Durham
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Casey C. Kopczynski
Sina Farsiu
1Department of Ophthalmology, Duke University
5Department of Biomedical Engineering, Duke University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
John R. Samples
6Washington State University Floyd Elson School of Medicine
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Pratap Challa
1Department of Ophthalmology, Duke University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
C. Ross Ethier
2Department of Biomedical Engineering, Georgia Institute of Technology/Emory University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • For correspondence: dan.stamer@duke.edu ross.ethier@bme.gatech.edu
W. Daniel Stamer
1Department of Ophthalmology, Duke University
5Department of Biomedical Engineering, Duke University
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for W. Daniel Stamer
  • For correspondence: dan.stamer@duke.edu ross.ethier@bme.gatech.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Preview PDF
Loading

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, 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.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
Back to top
PreviousNext
Posted July 17, 2020.
Download PDF
Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
Antifibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
Antifibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis
Guorong Li, Chanyoung Lee, A. Thomas Read, Ke Wang, Iris Navarro, Jenny Cui, Katherine M. Young, Rahul Gorijavolu, Todd Sulchek, Casey C. Kopczynski, Sina Farsiu, John R. Samples, Pratap Challa, C. Ross Ethier, W. Daniel Stamer
bioRxiv 2020.07.17.208207; doi: https://doi.org/10.1101/2020.07.17.208207
Digg logo Reddit logo Twitter logo Facebook logo Google logo LinkedIn logo Mendeley logo
Citation Tools
Antifibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis
Guorong Li, Chanyoung Lee, A. Thomas Read, Ke Wang, Iris Navarro, Jenny Cui, Katherine M. Young, Rahul Gorijavolu, Todd Sulchek, Casey C. Kopczynski, Sina Farsiu, John R. Samples, Pratap Challa, C. Ross Ethier, W. Daniel Stamer
bioRxiv 2020.07.17.208207; doi: https://doi.org/10.1101/2020.07.17.208207

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Physiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (3602)
  • Biochemistry (7567)
  • Bioengineering (5522)
  • Bioinformatics (20782)
  • Biophysics (10325)
  • Cancer Biology (7978)
  • Cell Biology (11635)
  • Clinical Trials (138)
  • Developmental Biology (6602)
  • Ecology (10200)
  • Epidemiology (2065)
  • Evolutionary Biology (13611)
  • Genetics (9539)
  • Genomics (12844)
  • Immunology (7919)
  • Microbiology (19538)
  • Molecular Biology (7657)
  • Neuroscience (42081)
  • Paleontology (308)
  • Pathology (1257)
  • Pharmacology and Toxicology (2201)
  • Physiology (3267)
  • Plant Biology (7038)
  • Scientific Communication and Education (1294)
  • Synthetic Biology (1951)
  • Systems Biology (5426)
  • Zoology (1116)