[Impact of anti-VEGF therapy on the cellular microenvironment in retinal angiogenesis]

Various large-scale studies show the efficacy of anti-vascular endothelial growth factor (VEGF) therapy in treatment of retinal diseases. Based on the evidence, it is expected that this therapeutic strategy will be used widely for various retinal vascular diseases including diabetic retinopathy and retinal vein occlusion. Leukocyte infiltration is an important step that occurs during angiogenesis in inflammatory diseases. Various studies report that infiltrated leukocytes are a prerequisite for retinal angiogenesis, including diabetic retinopathy. Furthermore, the fibrovascular membrane (FVM) microenvironment consists of stromal components (extracellular matrix, myofibroblasts and leukocytes) supported by angiogenesis (endothelial cells and pericytes). The activity of proliferative diabetic retinopathy (PDR) is thought to be determined by the angiogenesis-assisted FVM microenvironment status. Recently, we investigated whether intravitreal anti-VEGF therapy modulates leukocyte infiltration in retinal angiogenesis using the surgically obtained FVM in pars plana vitrectomy with or without pretreatment with bevacizumab. The effect of anti-VEGF therapy on leukocyte infiltration was also examined with a mouse model of oxygen-induced retinopathy. Moreover, the impact of anti-VEGF therapy on endothelial cells, pericytes and myofibroblasts was also examined using the FVM. We could observe that anti-VEGF therapy blocked leukocyte infiltration as well as re-entry from the retina. The therapy also could induce the contraction of blood vessels, increasing the pericyte ratio and transforming growth factor-β expression in the FVM. Our data indicate anti-VEGF therapy could attain anti-inflammation, vessel contraction and vessel maturation, resulting in the resolution of retinal edema as well as the prevention of intraoperative hemorrhage.