Protective Effect of a Bispecific Fc-Fusion Protein on the Barrier of Human Retinal Pigment Epithelial Cells

Abstract

Introduction: The aim of the study was to evaluate the protective effects of IBI302, a bispecific Fc-fusion protein that theoretically can bind vascular endothelial growth factor (VEGF), complement C3b, and C4b in the barrier of the cultured human retinal pigment epithelial (hRPE) cells. Methods: Primary hRPE cells were isolated and cultured to monolayer barrier. hRPE monolayers were divided into the PBS control group, VEGF-Trap group, complement receptor 1 (CR1) group, and IBI302 group. Identification of hRPE cells, barrier function, inflammation factors, and immune response products was tested by immunofluorescent staining, transepithelial resistance (TER), and ELISA. Results: IBI302 treatment significantly improved the TER of the barrier of hRPE cells after complement-activated oxidative stress compared with the PBS control group, VEGF-Trap group, and CR1 group. The maximum effect of IBI302 on protecting hRPE cell viability was observed at the concentration of 1 μg/mL. The elevated expression of VEGF, chemokine (C-C Motif) ligand 2, C3a, C5a, and membrane attack complex was reduced by IBI302. Conclusion: IBI302 could protect the barrier function of hRPE cells. IBI302 might be a potentially effective drug for the RPE barrier-associated ocular diseases.