September 2016
Volume 57, Issue 12
Open Access
ARVO Annual Meeting Abstract  |   September 2016
ROCK Inhibitor HA1077: Potently Inhibits Corneal Fibrosis and Neovascularization
Author Affiliations & Notes
  • Michael K Fink
    Harry S. Truman Veterans Hospital, Columbia, Missouri, United States
    Veterinary Medicine & Surgery and Veterinary Pathology, University of Missouri, Columbia, Missouri, United States
  • Suneel Gupta
    Harry S. Truman Veterans Hospital, Columbia, Missouri, United States
    Veterinary Medicine & Surgery, University of Missouri, Columbia, Missouri, United States
  • Steven Ebers
    Harry S. Truman Veterans Hospital, Columbia, Missouri, United States
    Mason Eye Institute, University of Missouri, Columbia, Missouri, United States
  • Ethan Crider
    Harry S. Truman Veterans Hospital, Columbia, Missouri, United States
    Mason Eye Institute, University of Missouri, Columbia, Missouri, United States
  • Michael Possin
    Harry S. Truman Veterans Hospital, Columbia, Missouri, United States
    Mason Eye Institute, University of Missouri, Columbia, Missouri, United States
  • Elizabeth A Giuliano
    Harry S. Truman Veterans Hospital, Columbia, Missouri, United States
    Veterinary Medicine & Surgery, University of Missouri, Columbia, Missouri, United States
  • Prashant Rajiv Sinha
    Harry S. Truman Veterans Hospital, Columbia, Missouri, United States
    Veterinary Medicine & Surgery, University of Missouri, Columbia, Missouri, United States
  • Frank G. Rieger
    Harry S. Truman Veterans Hospital, Columbia, Missouri, United States
    Mason Eye Institute, University of Missouri, Columbia, Missouri, United States
  • Rajiv R Mohan
    Harry S. Truman Veterans Hospital, Columbia, Missouri, United States
    Veterinary Medicine & Surgery, Biomedical Sciences, Veterinary Pathology, and Mason Eye Institute , University of Missouri , Columbia, Missouri, United States
  • Footnotes
    Commercial Relationships   Michael Fink, None; Suneel Gupta, None; Steven Ebers, None; Ethan Crider, None; Michael Possin, None; Elizabeth Giuliano, None; Prashant Sinha, None; Frank Rieger, None; Rajiv Mohan, None
  • Footnotes
    Support  University of Missouri Ruth M. Kraeuchi Ophthalmology Endowment Fund, partially from NIH/NEI R01EY17294 and Veterans Health Affairs 1I01BX00035701
Investigative Ophthalmology & Visual Science September 2016, Vol.57, No Pagination Specified. doi:
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      Michael K Fink, Suneel Gupta, Steven Ebers, Ethan Crider, Michael Possin, Elizabeth A Giuliano, Prashant Rajiv Sinha, Frank G. Rieger, Rajiv R Mohan; ROCK Inhibitor HA1077: Potently Inhibits Corneal Fibrosis and Neovascularization. Invest. Ophthalmol. Vis. Sci. 201657(12):.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Rho associated Kinase (ROCK) pathways regulate cellular proliferation, migration, adhesion, wound healing, fibrosis, and angiogenesis in vivo. We tested the postulate that topical ROCK inhibitor HA1077 application to the eye will attenuate corneal fibrosis and neovascularization in vivo in a rabbit disease model by preventing exuberant wound healing.

Methods : Twelve New Zealand White rabbits were used under IACUC protocol. Corneal fibrosis and neovascularization (CNV) were produced by a single topical alkali (1N NaOH) application for 1min to the central cornea. Following corneal wounding, animals were divided into two groups: Group-1 served as controls and received 50uL Balanced Salt Solution (BSS) topically twice daily for 3 days. Group-2 served as treatment cohort and received 50uL HA1077 (3nM) topically twice daily for 3 days. Contralateral untreated eyes served as negative controls. Serial slit- and stereomicroscopy evaluated for the presence and degree of ocular inflammation, corneal edema, and corneal opacity. Intraocular pressures were recorded with an applanation tonometer. Corneas were harvested on day-14 with H&E and immunofluorescence staining employed to characterize levels of fibrosis, CNV, inflammation, and apoptosis.

Results : Biomicroscopy detected a significant decrease (~2.8 fold; p<0.01) in corneal fibrosis and CNV in eyes treated with HA1077 compared to BSS-treated controls. Further, HA1077-treated corneas showed significant decreases in fibrosis markers (smooth muscle actin, fibronectin, and F-actin; 55-60%; p<0.0001), and did not exhibit significantly increased numbers of CD11b+ (2-11%) or TUNEL+ (0-5%) cells compared to BSS-treated controls during immunofluorescence analyses. A substantial decrease in CNV was also noted in HA1077-treated eyes as compared to BSS-treated controls (quantification pending). Clinical eye examinations and histological evaluation did not reveal evidence of acute toxicity from HA1077 topical application.

Conclusions : ROCK inhibitor HA1077 is a viable option for treating corneal fibrosis and neovascularization resulting from chemical injuries. Additional in vivo analysis is warranted.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.

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