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Topical Rho-Associated Protein Kinase Inhibitor HA1077 Reduces Rabbit Corneal Fibrosis and Neovascularization In

Michael K Fink1,2,3, Suneel Gupta1,2, Rajnish Kumar1,2

  • 1Harry S. Truman Memorial Veterans' Hospital, Columbia, Missouri, USA.

Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics
|December 30, 2025
PubMed
Summary
This summary is machine-generated.

Topical HA1077 effectively reduces corneal fibrosis and neovascularization in rabbits after alkali injury. This Rho-associated kinase inhibitor is well-tolerated, showing promise for treating fibrotic and vascularized corneal wounds.

Keywords:
HA1077ROCK inhibitorcorneafibrosisneovascularizationwound healing

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Area of Science:

  • Ophthalmology
  • Cell Biology
  • Pharmacology

Background:

  • Rho-associated kinase (ROCK) plays a crucial role in regulating cellular processes like fibrosis and angiogenesis.
  • Corneal fibrosis and neovascularization (CNV) are significant challenges in ophthalmology, often leading to vision impairment.
  • Targeting ROCK pathways offers a potential therapeutic strategy for managing these conditions.

Purpose of the Study:

  • To evaluate the efficacy of topical HA1077, a ROCK inhibitor, in attenuating corneal fibrosis and CNV in a rabbit model.
  • To assess the safety and tolerability of HA1077 in the ocular environment.

Main Methods:

  • Alkali injury was induced in New Zealand White rabbits to provoke corneal fibrosis and CNV.
  • Eyes were treated with topical HA1077 (3 nM) or balanced salt solution (BSS) control.
  • Corneal haze, CNV, and histological markers (α-SMA, F-actin, endoglin) were assessed.
  • Cell viability, intraocular pressure (IOP), and apoptosis were evaluated.

Main Results:

  • Topical HA1077 significantly reduced corneal haze/fibrosis and CNV compared to controls (P < 0.0001).
  • Histological analysis showed decreased fibrotic markers, neovessels, and immune cell infiltration in HA1077-treated corneas.
  • HA1077 treatment did not affect cell viability at tested doses and maintained IOP within normal physiological ranges.
  • TUNEL assays confirmed the tolerability of the HA1077 regimen.

Conclusions:

  • The tested HA1077 dosage regimen is effective and tolerable for treating alkali-induced corneal fibrosis and CNV in rabbits.
  • ROCK inhibition presents a promising therapeutic avenue for fibrotic and vascularized corneal conditions.
  • Further dose-response studies are warranted to optimize HA1077 treatment for corneal wound healing.