Attenuation of Oxygen-Induced Neovascularization and Inflammation by Neutralizing VEGFA and/or ANG-2 With an Antibody.

Abstract

Neovascularization is a major cause of blindness in various retinal diseases, and inflammation aggravates the pathological and clinical conditions of these diseases. VEGFA or ANG-2 neutralizing antibodies have been used to block pathological neovascularization. In this work, the effects of intraocular administration of neutralizing antibodies against VEGFA, ANG-2, or bispecific to these two factors on pathological findings were examined in the oxygen-induced retinopathy (OIR) mouse model. At both postnatal day (P)17 and P19, anti-VEGFA and -ANG-2 administration suppressed neovascularization, and the bispecific antibody attenuated neovascularization more efficiently. However, oxygen-induced vaso-obliteration was not modified by these antibodies. Numbers of photoreceptor, amacrine, and bipolar cells were reduced in the OIR retina, and the antibodies reversed these changes. Microglia-specific gene expression increased in the OIR retina, and administration of the antibodies reduced the IBA1-positive area in the OIR retina, although these antibodies did not affect Iba1 gene expression. Labeled VEGFA and ANG-2 were found to be co-localized with microglia, suggesting that VEGFA and ANG-2 affect microglia activation directly. Taken together, neutralizing antibody to VEGFA or ANG-2 attenuated oxygen-induced neovascularization and inflammation, and the bispecific antibody more efficiently suppressed some features than the single antibody to VEGFA or ANG-2.