Evaluation of collagen-derived peptide (EB-203) for treating neovascular age-related macular degeneration

Abstract

Neovascular age-related macular degeneration has been one of the challenging ocular diseases due to severe ocular implications like vision loss. As a key protein factor, VEGF has been reported to be closely related to choroidal neovascularization (CNV) as a representative pathogenesis of neovascular AMD. Conventionally, anti-VEGF antibody therapeutics like aflibercept have been used for improving AMD via intravitreal (IVT) injection. However, it has been burdensome for patients to continue IVT therapies because of high costs and risk of complications inherent to the injection procedure itself, such as intraocular hemorrhage and elevated intraocular pressure. To date, various strategies imploying modified antibodies, gene-based approaches, and small molecules have been investigated based on an improved understanding of the underlying mechanisms of neovascular AMD. In the present study, a novel peptide has been investigated for its anti-angiogenic activity in AMD using EA.hy926 cells treated with cobalt chloride (CoCl₂) to simulate hypoxic conditions. EB-203 demonstrated reduced HIF-1α and VEGF expression in western blot analysis. Under hypoxic condition, tube formation, migration and invasion of endothelial cells were inhibited by EB-203 to the levels of control. Moreover, mouse AMD models intravitreally injected with 100 µg of EB-203 exhibited comparable improvement to aflibercept in vascular leakage and CNV area. Mouse models administered 5% or 10% EB-203 eyedrops in twice daily dosing showed the reduction of vascular leakage and CNV area significantly. These results suggest that EB-203 is a promising peptide-based therapeutic candidate for neovascular AMD.