Exosome-Mediated Delivery of an Anti-Angiogenic Peptide Inhibits Corneal Neovascularization via VDAC1 and Autophagy

Abstract

Background: Angiogenesis is a crucial reason for the poor prognosis of corneal diseases. KV11, an undecanoic peptide from Kringle Ⅴ domain derived from apolipoprotein(a) is identified to inhibit angiogenesis significantly. Given the poor permeability and instability of small peptide, we aim to use exosome and its anchoring peptide CP05 to deliver KV11 to alkali-burn cornea tissue and inhibit corneal neovascularization.Methods: In vitro, we tested the effect of EXO-KV11 on inhibition of angiogenesis with the method of tube formation, transwell migration assay and CCK-8. In vivo, we used subconjunctival injection of EXO-KV11 to the alkali-burn cornea-induced corneal neovascularization rat model and fluorescent angiography to directly detect the impact on corneal neovascularization. We also revealed the underlying mechanism by western blot.Results: EXO-KV11 was verified to suppress endothelial cells tube formation, migration and proliferation in vitro by tube formation assay, transwell migration assay and CCK-8 assy. EXO-KV11 was more efficiently delivered to cornea tissue and suppressed more corneal neovascularization in alkali burn-induced corneal neovascularization model. Furthermore, VDAC1 might be potential receptor for KV11 and KV11 stimulated PERK and blocked up autography flux.Conclusions: We used exosomes to delivery KV11 into cells and cornea tissue. We reported that EXO-KV11 could inhibit angiogenesis more than KV11 both in vitro and in vivo. Thus exosome-CP05 drug delivery system has promising prospect in the future.