Protection of leukemia inhibitory factor against high-glucose-induced human retinal endothelial cell dysfunction

Purpose In the study, we aimed to explore the mechanism of leukaemia inhibitory factor (LIF) affects hyperglycaemic induced retinopathy by regulating CaMKII-CREB pathway. Methods Human retinal endothelial cell (HRECs) induced by high glucose to simulate one of the pathogenesis in the diabetic retinopathy (DR) model. After LIF treatment, cell viability was detected by CCK-8 and apoptosis was detected by flow cytometry. Angiogenesis was detected by in vitro tube formation. The expression levels of inflammatory, angiogenesis related proteins and CaMKII-CREB were detected by western blot. The gene level of angiogenesis was detected by qRT-PCR. HE staining was used to detect pathological changes of retinopathy in diabetic mice after LIF treatment. Results Our results showed that LIF significantly increased hyperglycaemic-induced cell viability and inhibited apoptosis. Western blot results showed that LIF could down-regulate the expression levels of inflammatory cytokines such as IL-1 beta, IL-6 and TNF-alpha. In addition, angiogenesis of HRECs was inhibited by LIF in tubulisation experiments. LIF can down-regulate protein and gene levels of VEGF and HIF-1 alpha via western blot and qRT-PCR. In diabetic mice induced by STZ, LIF could down-regulate the protein level of VEGF, HIF-1 alpha, p-CaMKII and p-CREB, which suggest that LIF could inhibit retinal angiogenesis in diabetic mice. The results of HE staining showed that LIF could alleviate the damage of retinopathy in diabetic mice. Conclusion LIF could alleviate the damage of diabetic retinopathy by modulating the CaMKII/CREB signalling pathway to inhibit inflammatory response and angiogenesis.