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Mesenchymal Stem Cells Modulate Light-induced Activation of Retinal Microglia Through CX3CL1/CX3CR1 Signaling
Libin Huang1, Guoxing Xu1, Jian Guo1
1a Department of Ophthalmology , First Affiliated Hospital of Fujian Medical University , Fuzhou , China.
Purpose:
To evaluate the effect of CX3CL1/CX3CR1 signaling on the interaction between mesenchymal stem cells (MSCs) and retinal microglia.
Methods:
Supernatants of homogenized retina were harvested from light-damaged SD rats (ISHR) to stimulated retinal microglia. Stimulated microglia were cocultured with MSCs, CX3CL1 over-expressing MSCs (CX3CL1-MSCs) or CX3CL1-blocked MSCs (anti-CX3CL1-MSCs) for 24 hours, and their molecular and functional changes were examined. Moreover, soluble CX3CL1 was directly added to microglia cultures.
Results:
ISHR stimulation activated retinal microglia. MSCs coculture inhibited the protein expression of pro-inflammatory factors by activated microglia, increased the protein expression of neurotrophic factors, and was accompanied with upregulation of CX3CR1. Meanwhile, MSCs suppressed proliferative and migratory function of activated microglia, but promoted the phagocytic capability. These effects were strengthened by CX3CL1- MSCs, and reversed by anti-CX3CL1-MSCs. Soluble CX3CL1 could enhanced microglial migration.
Conclusions:
MSCs might restore homeostatic functions of retinal microglia responded to light damage mainly through CX3CL1/CX3CR1 signaling.
Insights
Mesenchymal stem cells (MSCs) restore retinal microglia function after light damage by modulating CX3CL1/CX3CR1 signaling. This interaction reduces inflammation and enhances neuroprotection, promoting visual health.
Area of Science:
- Ophthalmology
- Neuroscience
- Immunology
Background:
- Retinal microglia play a crucial role in maintaining visual homeostasis.
- Light-induced damage can activate microglia, leading to inflammation and neurodegeneration.
- Mesenchymal stem cells (MSCs) have immunomodulatory properties with potential therapeutic applications in retinal diseases.
Purpose of the Study:
- To investigate the role of CX3CL1/CX3CR1 signaling in the interaction between MSCs and retinal microglia.
- To determine how MSCs influence the function of light-damaged retinal microglia.
- To elucidate the therapeutic potential of MSCs in light-induced retinal injury.
Main Methods:
- Retinal microglia were stimulated with supernatants from light-damaged rat retinas.
- Stimulated microglia were co-cultured with MSCs, CX3CL1-overexpressing MSCs, or MSCs with blocked CX3CL1.
- Molecular and functional changes in microglia were analyzed, including cytokine expression and cell behavior.
Main Results:
- MSCs inhibited pro-inflammatory factors and increased neurotrophic factors in activated microglia.
- MSCs modulated microglial proliferation, migration, and phagocytosis.
- CX3CL1/CX3CR1 signaling significantly influenced the effects of MSCs on microglia, with enhanced effects seen with CX3CL1-overexpressing MSCs.
Conclusions:
- MSCs restore homeostatic functions of retinal microglia following light-induced damage.
- The CX3CL1/CX3CR1 signaling pathway is a key mechanism mediating MSC therapeutic effects on retinal microglia.
- Targeting this pathway holds promise for treating retinal inflammatory conditions.
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