Abstract
Purpose :
During diabetic retinopathy (DR), the inflammatory response depends on the polarization of retinal microglia/macrophages, triggering pro-inflammatory (M1) or anti-inflammatory (M2) activity. In this study, we aimed to determine the role of microglia/macrophages in vascular hyperpermeability through the tight junction complexes of retinal pigment epithelium, which is the outer blood-retinal barrier (BRB). Furthermore, we aimed to assess whether interleukin-10 (IL-10), a representative M2-inducer, can decrease microglia/macrophage activation and alleviate outer-BRB disruption.
Methods :
Immunocytochemistry, flow cytometry, western blot, trans-epithelial permeability assays, transepithelial electrical resistance (TEER) measurements, and real-time polymerase chain reaction (RT-PCR) were conducted to examine the influence of macrophage polarity on the structural and functional integrity of ARPE-19 cells under high glucose conditions. Then, immunofluorescence staining, fluorescence-labeled dextran vascular leakage test, and RT-PCR were conducted to evaluate whether M2 macrophage polarization induced by intravitreal IL-10 injection suppresses outer blood-retinal barrier disruption and vascular leakage in streptozotocin (STZ)-induced early diabetic retinopathy mouse model.
Results :
We found that modulation of macrophage polarization to M1 or M2 influences the structural and functional integrity of ARPE-19 cells in a co-culture system under high-glucose conditions. Furthermore, we found that both outer-BRB disruption and polarity changes of recruited microglia/macrophages occur during early-stage STZ-induced DR progression, and we also found that intravitreal injection of IL-10 induces a decreased M1/M2 polarization ratio of recruited microglia/macrophages in the RPE layer and effectively suppresses outer-BRB disruption, possibly due to NF-κB inactivation in early-stage STZ-induced diabetic mice.
Conclusions :
Modulation of microglia/macrophage-polarization by IL-10 administration during early-stage DR has a promising protective effect against outer-BRB disruption and vascular leakage, and provides a novel therapeutic target and insights for early intervention in DR.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.