Mesenchymal Stem Cells Modulate Light-induced Activation of Retinal Microglia Through CX3CL1/CX3CR1 Signaling.

To evaluate the effect of CX3CL1/CX3CR1 signaling on the interaction between mesenchymal stem cells (MSCs) and retinal microglia. 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. 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. MSCs might restore homeostatic functions of retinal microglia responded to light damage mainly through CX3CL1/CX3CR1 signaling.