Inhibition of Corneal Neovascularization with the Combination of Aflibercept and Plasmid Pigment Epithelium-Derived Factor-Synthetic Amphiphile INTeraction-18 Vector

Abstract

Aflibercept, a recent VEGF inhibitor, is a recombinant fusion protein consisting of portions of human VEGF receptors 1 and 2 extracellular domains, fused to the Fc portion of human IgG1 formulated as an iso-osmotic solution for intravitreal administration. In this study, we have estimated that the combination of aflibercept and plasmid pigment epithelium-derived factor-synthetic amphiphile INTeraction-18 (p-PEDF-SAINT-18) has a favorable antiangiogenic effect on corneal neovascularization (NV). Four groups (Group A: 0 μg + 0 μg, B: 0. 1μg + 0.1 μg, C: 1 μg + 1 μg, D: 10 μg + 10 μg) of aflibercept + p-PEDF-SAINT-18 were prepared and implanted into rat subconjunctival substantia propria 1.5 mm from the limbus on the temporal side. The 2 μg of p- bFGF-SAINT-18 were prepared and implanted into the rat corneal stroma 1.5mm from the limbus on the same side. Inhibition of NV was observed and quantified from day 1 to day 90. 18-kDa bFGF and VEGF protein expression was analyzed through biomicroscopic examination, western blot analysis and immunohistochemistry. No inhibition activity for normal limbal vessels was noted. Subconjunctival injection by a combination of aflibercept and p-PEDFSAINT-18 successfully inhibited corneal NV. Successful genes of bFGF and PEDF were expressed through western blot analysis; immunohistochemistry staining showed mild immune response for HLA-DR. We conclude that the combination of aflibercept and p-PEDF-SAINT-18 may have more potent and prolonged antiangiogenic effects, making it possible to reduce the frequency of subconjunctival aflibercept administration, while maintaining relatively high safety and low toxicity.