The protective effect of anti-VEGF-A/Ang-2 bispecific antibody on retinal vein occlusion model mice

Abstract

(233/250) Retinal vein occlusion (RVO) causes macular edema and retinal ischemia resulting in visual field and vision loss. A bispecific antibody that blocks VEGF-A and angiopoietin-2 (Ang-2) has been recently launched and applied clinically to treat macular edema, but the role of Ang-2 in the pathogenesis of RVO is still unclear. In this study, we investigated the effects of the anti-VEGF-A/anti-Ang-2 bispecific antibody (BsAb) in a murine RVO model. By using RVO model mice, the expression of Ang-2 gene and protein was examined in the retina through real-time qPCR and Western blotting, respectively. A significant increase in Ang-2 was detected 1 day after occlusion. Immediately after occlusion, control IgG 400 μg/mL, anti-VEGF-A antibody 200 μg/mL, anti-Ang-2 antibody 200 μg/mL, and BsAb 400 μg/mL were intravitreally administered at 2 μL. Visual function was examined using electroretinograms, and apoptosis was examined using TUNEL staining. Interestingly, BsAb partially suppressed the decrease in amplitude of a and b waves compared to control IgG. Anti-Ang-2 antibody and BsAb reduced apoptosis-positive cells 1 day after occlusion. Comprehensive gene expression profiles were also examined using RNA sequencing analysis. RNA sequencing analysis of the retinal tissues showed that BsAb suppressed expression of gene groups associated with inflammatory response and vascular development compared to anti-VEGF-A antibody. Taken together, higher expression of Ang-2 contributes to the pathophysiology of RVO, providing a possible mechanism for the efficacy of BsAb in suppressing retinal dysfunction in RVO.

Keywords: Angiopoietin-2; Apoptosis; Edema; Retina; VEGF; Visual function.