Inhibition of corneal neovascularization with plasmid pigment epithelium-derived factor (p-PEDF) delivered by synthetic amphiphile INTeraction-18 (SAINT-18) vector in an experimental model of rat corneal angiogenesis

Exp Eye Res. 2009 Nov;89(5):678-85. doi: 10.1016/j.exer.2009.06.021. Epub 2009 Jul 9.

Abstract

The use of Synthetic Amphiphile INTeraction-18 (SAINT-18) carrying plasmid pigment epithelium-derived factor (p-PEDF) as an anti-angiogenesis strategy to treat corneal neovascularization in a rat model was evaluated. Four partially dried forms (Group A: 0 microg, B: 0.1 microg, C: 1 microg, D: 10 microg) of a p-PEDF-SAINT-18 were prepared and implanted into the rat subconjunctival substantia propria 1.5 mm from the limbus at the temporal side. The 1 microg of plasmid-basic fibroblast growth factor--SAINT-18 (p-bFGF-SAINT-18) (1 microg) was prepared and implanted into the rat corneal stroma 1.5 mm from the limbus on the same side. Inhibition of neovascularization was observed and quantified from day 1 to day 60. PEDF (50-kDa) and bFGF (18-kDa) protein expression were analyzed by biomicroscopic examination, Western blot analysis, and immunohistochemistry. Gene expression in corneal and conjunctival tissue was observed as early as 3 days after gene transfer and stably lasted for over 3 months with minimal immune reaction. Subconjunctival injection of a highly efficient p-PEDF-SAINT-18 successfully inhibited corneal neovascularization. Successful gene expression of bFGF, PEDF and a mild immune response of HLA-DR were shown by immunohistochemistry staining. We concluded that SAINT-18 was capable of directly delivering genes to the ocular surface by way of subconjunctival injection, and delivered sustained, high levels of gene expression in vivo to inhibit angiogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Conjunctiva / metabolism*
  • Cornea / blood supply*
  • Cornea / immunology
  • Cornea / metabolism*
  • Corneal Neovascularization / genetics
  • Corneal Neovascularization / immunology
  • Corneal Neovascularization / metabolism
  • Corneal Neovascularization / pathology
  • Corneal Neovascularization / prevention & control*
  • Disease Models, Animal
  • Eye Proteins / biosynthesis*
  • Eye Proteins / genetics
  • Eye Proteins / immunology
  • Feasibility Studies
  • Fibroblast Growth Factor 2 / biosynthesis
  • Fibroblast Growth Factor 2 / genetics
  • Genetic Therapy / methods*
  • HLA-DR Antigens / immunology
  • Immunohistochemistry
  • Injections
  • Male
  • Nerve Growth Factors / biosynthesis*
  • Nerve Growth Factors / genetics
  • Nerve Growth Factors / immunology
  • Pyridinium Compounds / immunology
  • Pyridinium Compounds / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Serpins / biosynthesis*
  • Serpins / genetics
  • Serpins / immunology
  • Time Factors
  • Transfection*

Substances

  • 1-methyl-4-(9-dioleyl)methylpyridinium
  • Eye Proteins
  • HLA-DR Antigens
  • Nerve Growth Factors
  • Pyridinium Compounds
  • Serpins
  • pigment epithelium-derived factor
  • Fibroblast Growth Factor 2