Effects of VEGFA and ANGPT2 Antibodies on the Activation of Microglia in the Early Stages of Streptozotocin-Induced Pathogenesis of Diabetic Retinopathy

Abstract

Diabetic retinopathy (DR) is known as a microvascular complication, in which various inflammatory symptoms, including activation of microglia, are observed. A model of hyperglycemia resembling type 1 diabetes mellitus (DM) induced in mice by intraperitoneal injection of streptozotocin (STZ) has been widely used. We examined the effects of anti- vascular endothelial growth factor A (VEGFA) and anti-angiopoietin-2 (ANGPT2) antibodies in addition to a bispecific antibody against VEGFA and ANGPT2 by intravitreously administrated to the eyes on early signs, especially the activation of microglia in STZ-treated mice eyes. After 14 weeks of STZ administration, alterations in activity by ERG and CD31 staining patterns were not observed. Although a difference in the number of microglia in the retina between normal and STZ-model retinas was not observed, the morphology of microglia had changed from ramified in control to amoeboid shape in STZ model at 4 days after the antibodies injection. Detailed morphological examination showed decreases in area, ramification index, and tree length in the STZ-model retinas compared with normal retinas. Recovery from these decreases was demonstrated mainly by the administration of the bispecific antibody. These results suggest that anti-VEGFA/ANGPT2 therapy may suppress the activation of microglia in the early stages of DR.