Enhancing fractalkine/CX3CR1 signalling pathway can reduce neuroinflammation by attenuating microglia activation in experimental diabetic retinopathy

The concept of diabetic retinopathy (DR) has been extended from microvascular disease to neurovascular disease in which microglia activation plays a remarkable role. Fractalkine (FKN)/CX3CR1 is reported to regulate microglia activation in central nervous system diseases. To characterize the effect of FKN on microglia activation in DR, we employed streptozotocin-induced diabetic rats, glyoxal-treated R28 cells and hypoxia-treated BV2 cells to mimic diabetic conditions and explored retinal neuronal apoptosis, reactive oxygen species (ROS), as well as the expressions of FKN, Iba-1, TSPO, NF-kappa B, Nrf2 and inflammation-related cytokines. The results showed that FKN expression declined with diabetes progression and in glyoxal-treated R28 cells. Compared with normal control, retinal microglia activation and inflammatory factors surged in both diabetic rat retinas and hypoxia-treated microglia, which was largely dampened by FKN. The NF-kappa B and Nrf2 expressions and intracellular ROS were up-regulated in hypoxia-treated microglia compared with that in normoxia control, and FKN significantly inhibited NF-kappa B activation, activated Nrf2 pathway and decreased intracellular ROS. In conclusion, the results demonstrated that FKN deactivated microglia via inhibiting NF-kappa B pathway and activating Nrf2 pathway, thus to reduce the production of inflammation-related cytokines and ROS, and protect the retina from diabetes insult.

Automated summary

The study found that Fractalkine (FKN) can deactivate microglia in diabetic retinopathy by inhibiting the NF-kappa B pathway and activating the Nrf2 pathway, thereby reducing the production of inflammation-related cytokines and reactive oxygen species.