M1 and M2 Macrophage in Proliferative Diabetic Retinopathy: Altered Macrophage Polarization by Bevacizumab in Diabetic Fibrovascular Membranes

Abstract

Purpose: Macrophage is an important component in the pathogenesis of diabetic retinopathy. Recently, it is reported that macrophage phenotype (M1 and M2) can be switched by microenvironment of diseases such as cancer or atherosclerosis. However, macrophage phenotype in diabetic retinopathy remains elusive. The purpose of this project is to evaluate macrophage phenotype in diabetic fibrovascular membranes (FVMs) and the effect by Intravitreal bevacizumab (IVB).

Methods: Immunohistological studies with Abs of pan-macrophage marker (CD68), M1 macrophage marker (CD80) and M2 macrophage marker (CD206) were performed on 24 surgical specimens obtained during a pars plana vitrectomy from 9 IVB-treated eyes, while 15 remained untreated. Cellular density of each macrophage phenotype was quantitatively-analyzed in the two groups.

Results: We could observe macrophages including M1 and M2 macrophages in FVMs of PDR patients, and the number of M2 macrophages could be present more than M1 macrophages. IVB could not affect the number of M2 macrophages as well as total macrophages in the FVMs, whereas M1 macrophage number in IVB-treated FVMs was less than untreated FVMs. The ratio of macrophage phenotype (M2/M1) in IVB-treated FVM was significantly higher than untreated FVMs.

Conclusions: Macrophage phenotype might be polarized to be M2 dominant by the disease microenvironment in FVMs of PDR. Furthermore, the effect of IVB on the pathogenesis of PDR could be due to M2 macrophage polarization in PDR patients.

Keywords: 499 diabetic retinopathy