Evaluation of Collagen-Derived peptide (EB-203) for Treating Wet Age-Related Macular Degeneration

Wet 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 with the choroid neovascularization (CNV) as a representative pathogenesis of wet AMD. Conventionally, anti-VEGF antibody therapeutics like aflibercept have been used for improving AMD with a route of intravitreal (IVT) injection. However, there have been burdensome for patients to continue the IVT therapies because of high costs and ocular inflammation issues. Up to date, different strategies using modified antibodies, genes or small molecules have been investigated along with the underlying mechanisms of wet 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. In result, the peptide, EB-203, showed inhibition on Hif-1α and VEGF expression in western blot. Under the hypoxia condition, tube formation of the endothelial cells was interfered with EB-203 and further, migration and invasion of endothelial cells were inhibited by EB-203 to the levels of control. Moreover, mouse AMD models intravitreally injected by EB-203 at some drug concentrations exhibited comparable improvement to aflibercept in vascular leakage and CNV area. Mouse models administered by 5% or 10% EB-203 eyedrops in twice daily dosing showed the reduction of vascular leakage and CNV area significantly. These results demonstrated that the peptide drug can contribute to improve wet AMD complications and visual acuity as an anti-VEGF inhibitor.