Spleen Tyrosine Kinase Mediates Microglial Activation in Mice With Diabetic Retinopathy

PURPOSE: Diabetic retinopathy (DR) is a leading cause of blindness in developed countries, in which microglial activation is involved. However, the mechanism of microglial activation in DR remains largely unknown. METHODS: We used Cx3cr1(CreERT2); Syk(fl/fl) mice to knockout microglial spleen tyrosine kinase (Syk) in the retina of mice (cKO mice) after streptozotocin injection to induce diabetes. We also isolated primary retinal microglia from wild-type and cKO mice, respectively, to explore the role of microglial Syk in DR. RESULTS: The deletion of microglial Syk in the retina of mice or in the primary retinal microglia inhibited microglial activation and inflammatory response, eventually leading to the improvement of DR by regulating the expressions of interferon regulatory factor 8 (Irf8) and Pu.1 both in vivo and in vitro. CONCLUSIONS: The deletion of microglial Syk in the retina effectively ameliorated microglial activation-induced DR, suggesting the potential of microglial Syk as a therapeutic target for DR. TRANSLATIONAL RELEVANCE: Microglial spleen tyrosine kinase might serve as a potential therapeutic target for diabetic retinopathy.