KH906, a recombinant human VEGF receptor fusion protein, is a new effective topical treatment for corneal neovascularization

Mol Vis. 2011 Mar 25:17:797-803.

Abstract

Purpose: The purpose of the current study was to investigate the effect of topical administration of KH906 on corneal neovascularization (NV).

Methods: To induce corneal neovascularization, chemical cauterization of the corneas of the right eyes of forty-eight New Zealand white rabbits was performed by touching the central cornea with an 8-mm-diameter NaOH-soaked Whatman filter paper for 60 s. On the next day after modeling, the rabbits were randomly and equally divided into six groups: PBS control group, 0.1% dexamethasone group, 10 mg/ml Avastin group, 5 mg/ml KH906 group, 10 mg/ml KH906 group, and 20 mg/ml KH906 group. The rabbits in the six groups received topical administration of 50 μl of the different solutions on the cornea four times per day for 14 days. Corneal neovascularization was analyzed by slit-lamp biomicroscopy 10 and 14 days after chemical cauterization. Corneal fluorescein staining was performed to evaluate the extent of corneal epithelial defect on the 7th, 10th, and 14th days. The VEGF level of the cornea was evaluated by ELISA assay.

Results: On the 10th and 14th days after chemical cauterization, the length of the longest new vessel and the areas of corneal neovascularization in all KH906-treated groups were significantly reduced compared to those of the PBS-treated group (p<0.05). The VEGF level of the cornea in all KH906-treated groups was significantly decreased compared to that of the PBS-treated group (p<0.05). Corneal fluorescein staining showed that KH906 had no effect on corneal epithelial healing.

Conclusions: Topical administration of KH906 significantly inhibited alkali burn-induced corneal neovascularization in rabbits. The new eye drops of KH906 may have a broad application for human corneal neovascularization in the near future.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Topical
  • Angiogenesis Inhibitors / administration & dosage
  • Angiogenesis Inhibitors / genetics
  • Angiogenesis Inhibitors / metabolism*
  • Angiogenesis Inhibitors / therapeutic use*
  • Animals
  • Burns, Chemical / drug therapy
  • Burns, Chemical / pathology
  • Cornea / drug effects
  • Cornea / pathology
  • Corneal Neovascularization / chemically induced
  • Corneal Neovascularization / drug therapy*
  • Corneal Neovascularization / metabolism
  • Fluorescein / analysis
  • Humans
  • Ophthalmic Solutions / administration & dosage
  • Ophthalmic Solutions / therapeutic use
  • Rabbits
  • Receptors, Vascular Endothelial Growth Factor / administration & dosage
  • Receptors, Vascular Endothelial Growth Factor / genetics
  • Receptors, Vascular Endothelial Growth Factor / metabolism*
  • Receptors, Vascular Endothelial Growth Factor / therapeutic use*
  • Recombinant Fusion Proteins / administration & dosage
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism*
  • Recombinant Fusion Proteins / therapeutic use*
  • Sodium Hydroxide / adverse effects
  • Treatment Outcome
  • Vascular Endothelial Growth Factors / antagonists & inhibitors
  • Vascular Endothelial Growth Factors / metabolism

Substances

  • Angiogenesis Inhibitors
  • Ophthalmic Solutions
  • Recombinant Fusion Proteins
  • Vascular Endothelial Growth Factors
  • Sodium Hydroxide
  • Receptors, Vascular Endothelial Growth Factor
  • Fluorescein