Enhancing fractalkine/CX3CR1 signalling pathway can reduce neuroinflammation by attenuating microglia activation in experimental diabetic retinopathy
Related Experiment Video
Updated: Oct 6, 2025
Characterization of a Novel Human Organotypic Retinal Culture Technique
Published on: June 9, 2021
Mengmeng Jiang1, Hai Xie2, Chaoyang Zhang3,4
1Department of Ophthalmology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Abstract:
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-κB, 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-κB and Nrf2 expressions and intracellular ROS were up-regulated in hypoxia-treated microglia compared with that in normoxia control, and FKN significantly inhibited NF-κB activation, activated Nrf2 pathway and decreased intracellular ROS. In conclusion, the results demonstrated that FKN deactivated microglia via inhibiting NF-κB pathway and activating Nrf2 pathway, thus to reduce the production of inflammation-related cytokines and ROS, and protect the retina from diabetes insult.
Insights
Fractalkine (FKN) levels decrease in diabetic retinopathy (DR), leading to microglia activation. FKN protects the retina by deactivating microglia, reducing inflammation and oxidative stress.
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- Diabetic retinopathy (DR) is increasingly viewed as a neurovascular disease involving microglia activation.
- Fractalkine (FKN)/CX3CR1 signaling regulates microglia in central nervous system disorders.
Purpose of the Study:
- To investigate the role of FKN in microglia activation within the context of diabetic retinopathy.
- To explore FKN's impact on retinal neuronal apoptosis, oxidative stress, and inflammatory markers in DR models.
Main Methods:
- Utilized streptozotocin-induced diabetic rats, glyoxal-treated R28 cells, and hypoxia-treated BV2 cells to model diabetic conditions.
- Assessed expressions of FKN, Iba-1, TSPO, NF-κB, Nrf2, inflammatory cytokines, and reactive oxygen species (ROS).
Main Results:
- FKN expression decreased with diabetes progression and in cellular models.
- Diabetic conditions and hypoxia increased retinal microglia activation and inflammatory factors, which FKN mitigated.
- FKN inhibited NF-κB activation, promoted Nrf2 pathway activation, and reduced intracellular ROS in microglia.
Conclusions:
- FKN deactivates microglia in diabetic retinopathy by modulating the NF-κB and Nrf2 pathways.
- This action reduces the production of inflammatory cytokines and ROS, offering retinal protection against diabetic damage.
