Inhibition of Pathologic Corneal Neovascularization by Topical Application of a Novel Peptide In Vivo

Cornea. 2015 Oct;34(10):1295-302. doi: 10.1097/ICO.0000000000000548.

Abstract

Purpose: To investigate the antiangiogenic effect of topical application of H-KI20, a novel 20-amino acid peptide from the hepatocyte growth factor, on 2 animal models of corneal neovascularization (NV), and its possible toxic effects on the cornea and conjunctiva.

Methods: The antiangiogenic effect of topical H-KI20 in vivo was studied on corneal NV induced by a mouse corneal micropocket assay and rat intrastromal suture model. In each model, H-KI20, scrambled control peptide H-KI20S, bevacizumab, and phosphate buffer solution (PBS) were applied topically 4 times a day. Corneal NV was examined, photographed, and analyzed. Histological analysis of the corneas was performed. Tear film breakup time and gross and histological examinations were used to study the possible toxicity of topical H-KI20.

Results: Topical application of H-KI20 significantly inhibited corneal NV induced by vascular endothelial growth factor (VEGF), and intrastromal suture (P < 0.01 vs. the PBS group), and the area of corneal NV was suppressed by 80.3% and 83.6%, respectively (PBS group as 100%). No significant difference was found between 1.0 mg/mL H-KI20 and 10 mg/mL bevacizumab (P > 0.05). Both hematoxylin and eosin and CD34 staining revealed fewer new blood vessels in the H-KI20 and bevacizumab groups. Tear film breakup time and histological examinations showed that H-KI20 had no obvious toxic effects on the cornea and conjunctiva in vivo.

Conclusions: The novel peptide H-KI20 is an effective and safe inhibitor of corneal NV. It may provide a promising alternative for ocular topical antiangiogenic therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Amino Acid Sequence
  • Angiogenesis Inhibitors / chemical synthesis
  • Angiogenesis Inhibitors / therapeutic use*
  • Angiogenesis Inhibitors / toxicity
  • Animals
  • Bevacizumab / therapeutic use
  • Conjunctiva / drug effects
  • Cornea / drug effects
  • Corneal Neovascularization / pathology
  • Corneal Neovascularization / prevention & control*
  • Disease Models, Animal*
  • Hepatocyte Growth Factor / chemical synthesis
  • Hepatocyte Growth Factor / chemistry
  • Hepatocyte Growth Factor / therapeutic use*
  • Hepatocyte Growth Factor / toxicity
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Ophthalmic Solutions
  • Peptide Fragments / chemical synthesis
  • Peptide Fragments / therapeutic use*
  • Peptide Fragments / toxicity
  • Peptides / chemical synthesis
  • Peptides / therapeutic use
  • Peptides / toxicity
  • Rats
  • Rats, Sprague-Dawley
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors

Substances

  • Angiogenesis Inhibitors
  • H-KI20 peptide
  • Ophthalmic Solutions
  • Peptide Fragments
  • Peptides
  • Vascular Endothelial Growth Factor A
  • vascular endothelial growth factor A, mouse
  • vascular endothelial growth factor A, rat
  • Bevacizumab
  • Hepatocyte Growth Factor