Abstract
Neovascularization (NV) of the cornea disrupts vision which leads to blindness. Investigation of antiangiogenic, slow-release and biocompatible approaches for treating corneal NV is of great importance. We designed an eye drop formulation containing gelatin/epigallocatechin-3-gallate (EGCG) nanoparticles (NPs) for targeted therapy in corneal NV. Gelatin-EGCG self-assembled NPs with hyaluronic acid (HA) coating on its surface (named GEH) and hyaluronic acid conjugated with arginine-glycine-aspartic acid (RGD) (GEH-RGD) were synthesized. Human umbilical vein endothelial cells (HUVECs) were used to evaluate the antiangiogenic effect of GEH-RGD NPs in vitro. Moreover, a mouse model of chemical corneal cauterization was employed to evaluate the antiangiogenic effects of GEH-RGD NPs in vivo. GEH-RGD NP treatment significantly reduced endothelial cell tube formation and inhibited metalloproteinase (MMP)-2 and MMP-9 activity in HUVECs in vitro. Topical application of GEH-RGD NPs (once daily for a week) significantly attenuated the formation of pathological vessels in the mouse cornea after chemical cauterization. Reduction in both vascular endothelial growth factor (VEGF) and MMP-9 protein in the GEH-RGD NP-treated cauterized corneas was observed. These results confirm the molecular mechanism of the antiangiogenic effect of GEH-RGD NPs in suppressing pathological corneal NV.
Highlights
Corneal neovascularization (NV) is the formation of new vessels from pre-existing vascular structures in the transparent cornea, resulting from a variety of ocular pathologic conditions which are detrimental to vision [1,2,3,4]
We reported that RGD peptide modified nanoparticles (NPs) can deliver EGCG to human umbilical vein endothelial cells (HUVEC) [20]
The surface of NPs was decorated with hyaluronic acid (HA) or HA-RGD, termed GEH and GEH-RGD, respectively (Figure 1A)
Summary
Corneal neovascularization (NV) is the formation of new vessels from pre-existing vascular structures in the transparent cornea, resulting from a variety of ocular pathologic conditions which are detrimental to vision [1,2,3,4]. We reported that RGD peptide modified nanoparticles (NPs) can deliver EGCG to human umbilical vein endothelial cells (HUVEC) [20]. We applied RGD-modified NPs containing EGCG as an eye drop formula for the treatment of corneal NV. In addition to in vitro study, we employed a mouse model of chemical cauterization-induced corneal NV to investigate the antiangiogenic effect of RGD-modified NPs and their underlying molecular mechanisms in corneal NV inhibition in vivo. GEH-RGD NPs with EGCG and free-form EGCG were freshly prepared for the experiments
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