Intravitreal Anti-vegf Therapy Blocks Inflammatory Cell Infiltration And Re-entry Into The Circulation In Retinal Angiogenesis

Abstract

Purpose: : Anti-VEGF-A antibody (Ab) (e.g. bevacizumab, ranibizumab) is widely used as a treatment against retinal angiogenesis and edema. The purpose of this study was to evaluate whether intravitreal anti-VEGF-A Ab injection modulates inflammatory cells in retinal angiogenesis.

Methods: : To investigate whether intravitreal bevacizumab injection affects the number of inflammatory cells in proliferative diabetic retinopathy (PDR) membranes in patients, immunohistochemical staining with CD45 Ab (pan-leukocyte marker) was performed using the surgically obtained membranes in pars plana vitrectomy with or without pretreatment with bevacizumab. To check whether anti-VEGF-A Ab affects leukocytes going in and out of blood vessels during retinal angiogenesis, we performed our novel leukocyte transmigration assay and CD45 immunostaining in a mouse model of oxygen-induced retinopathy (OIR).

Results: : Our new imaging approach revealed that intravitreal injection of anti-VEGF-A Ab blocks leukocyte infiltration as well as angiogenesis. The Ab injection inhibited leukocyte transmigration before affecting angiogenenic area. CD45 staining showed no significant difference in leukocyte number in angiogenic retina or human PDR membranes between anti-VEGF-A Ab injected and control group. Furthermore, VEGF-A inhibition also affected leukocyte going out from retina.

Conclusions: : Intravitreal injection of anti-VEGF-A Ab could inhibit leukocyte trafficking in retina, suggesting anti-VEGF-A therapy could serve to retinal inflammation.

Keywords: vascular endothelial growth factor • inflammation • diabetic retinopathy