期刊
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
卷 26, 期 4, 页码 1229-1244出版社
WILEY
DOI: 10.1111/jcmm.17179
关键词
diabetic retinopathy; fractalkine; microglia; neuroinflammation
资金
- National Natural Science Foundation of China [82171061, 82171062, 81570852]
- Science and Technology Commission of Shanghai Municipality [18411953400, 19495800700]
- National Major Scientific and Technological Special Project for 'Significant New Drugs Development' during the Thirtieth Five-year Plan Period [2019ZX09301113]
- Ministry of Science and Technology of China [2020YFA0113101]
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.
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.
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