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

Chien Neng Kuo, Lin Cheng Yang, Cheng Ta Yang, Chien Hsiung Lai, Miao Fen Chen, Chung Yi Chen, Chi Hung Chen, Pei Chang Wu, Hsi Kung Kou, Yung Jen Chen, Chia Hui Hung*, Chong Bin Tsai

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

24 Scopus citations

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 μg, B: 0.1 μg, C: 1 μg, D: 10 μg) 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 μg of plasmid-basic fibroblast growth factor--SAINT-18 (p-bFGF-SAINT-18) (1 μg) 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. Crown

Original languageEnglish
Pages (from-to)678-685
Number of pages8
JournalExperimental Eye Research
Volume89
Issue number5
DOIs
StatePublished - 11 2009

Keywords

  • SAINT-18 (synthetic amphiphile interaction-18), 1-methyl-4-(cis-9-dioleyl)methylpyridinium-chloride
  • angiogenesis
  • cornea
  • fibroblast growth factor
  • nonviral vector
  • pigment epithelium-derived factor

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