Inhibition of corneal neovascularization with the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18) vector in a rat corneal experimental angiogenesis model

Int J Mol Sci. 2013 Apr 16;14(4):8291-305. doi: 10.3390/ijms14048291.

Abstract

Bevacizumab, a 149-kDa protein, is a recombinant humanized monoclonal antibody to VEGF. PEDF, a 50-kDa glycoprotein, has demonstrated anti-vasopermeability properties. In this study, we demonstrated that the combination of bevacizumab and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18(p-PEDF-SAINT-18) has a favorable antiangiogenic effect on corneal NV. Four groups(Group A: 0 μg + 0 μg, B: 0.1 μg + 0.1 μg, C: 1 μg + 1 μg, and D: 10 μg + 10 μg) of bevacizumab + p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. Then, 1 μgof p-bFGF-SAINT-18 was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. The inhibition of NV was observed and quantified from days 1 to 60. Biomicroscopic examination, western blot analysis and immunohistochemistry were used to analyze the 18-kDa bFGF, 50-kDa PEDF and VEGF protein expression. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection with the combination of bevacizumab and p-PEDF-SAINT-18 successfully inhibited corneal NV.The bFGF and PEDF genes were successfully expressed as shown by western blot analysis,and a mild immune response to HLA-DR was shown by immunohistochemistry. We concluded that the combination of bevacizumab and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival bevacizumab administration combined with a relatively safe profile and low toxicity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiogenesis Inhibitors / administration & dosage
  • Animals
  • Antibodies, Monoclonal, Humanized / administration & dosage*
  • Bevacizumab
  • Corneal Neovascularization / genetics
  • Corneal Neovascularization / pathology
  • Corneal Neovascularization / prevention & control*
  • Disease Models, Animal
  • Eye Proteins / genetics*
  • Eye Proteins / metabolism
  • Fibroblast Growth Factor 2 / genetics
  • Fibroblast Growth Factor 2 / metabolism
  • Gene Expression
  • Male
  • Nerve Growth Factors / genetics*
  • Nerve Growth Factors / metabolism
  • Plasmids / administration & dosage
  • Plasmids / genetics
  • Pyridinium Compounds / administration & dosage*
  • Rats
  • Rats, Sprague-Dawley
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Serpins / genetics*
  • Serpins / metabolism
  • Surface-Active Agents / administration & dosage
  • Transfection
  • Vascular Endothelial Growth Factor A / antagonists & inhibitors
  • Vascular Endothelial Growth Factor A / genetics
  • Vascular Endothelial Growth Factor A / metabolism

Substances

  • 1-methyl-4-(9-dioleyl)methylpyridinium
  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal, Humanized
  • Eye Proteins
  • Nerve Growth Factors
  • Pyridinium Compounds
  • Recombinant Proteins
  • Serpins
  • Surface-Active Agents
  • Vascular Endothelial Growth Factor A
  • pigment epithelium-derived factor
  • vascular endothelial growth factor A, rat
  • Fibroblast Growth Factor 2
  • Bevacizumab