Interaction between microglia and retinal pigment epithelial cells determines the integrity of outer blood ‐retinal barrier in diabetic retinopathy

In this study, we aimed to investigate the mechanisms of the outer BRB disruption regarding the interaction between RPE an d microglia. In mice with high‐fat diet‐induced obesity and streptozotocin‐induced hyperglycemia, microglia accumulated on the RPE layer, as in those after intravitreal injection of interleukin (IL)‐6, which is elevated in ocular fluids of patients with diabetic retinopathy. Although IL‐6 did not directly affect the levels of zonula occludens (ZO)‐1 and occludin in RPE cells, IL‐6 increasedVEGFA mRNA in RPE cells to recruit microglial cells. In microglial cells, IL ‐6 upregulated the mRNA levels ofMCP1,MIP1A, andMIP1B, to amplify the recruitment of microglial cells. In this manner, IL ‐6 modulated RPE and microglial cells to attract microglial cells on RPE cells. Furthermore, IL‐6‐treated microglial cells produced and secreted tumor necrosis factor (TNF)‐α, which activated NF‐κB and decreased the levels of ZO‐1 in RPE cells. As STAT3 inhibition reversed the effects of IL‐6‐treated microglial cells on the RPE monolayerin vitro, it reduced the recruitment of microglial cells and the production of TNF ‐α in RPE tissues in streptozotocin‐treated mice. Taken together, IL‐6‐treated RPE and microglial cells amplified the recruitment of microglial cells and IL‐6‐treated microglial cells produced TNF‐α to disrupt the outer BRB in diabetic retinopathy.
Source: Glia - Category: Neurology Authors: Tags: RESEARCH ARTICLE Source Type: research