Anti-CXCL10 monoclonal antibody therapy protects against the diabetic retinopathy in the mouse model induced by streptozotocin

• Diabetic retinopathy (DR) mice present up-regulated CXCL10 in retina. • Anti-CXCL10 mAb improve retinal pathology of streptozotocin (STZ)-induced DR mice. • Inhibiting CXCL10 mitigates inflammation and oxidative stress in the retina of DR. • CXCL10 knockdown reduce acellular capillaries in the retina of DR mice. To explore the effect of CXC chemokine CXCL10 in the mice with diabetic retinopathy (DR). DR models were constructed on mice via injection of streptozotocin (STZ). At 3 weeks of STZ, mice were treated with anti-CXCL10 monoclonal antibodies (mAb)/control mAb, and a series of experiments were then conducted at 6 weeks of STZ, including HE staining, western blotting, retinal trypsin digestion, real-time qPCR and enzyme-linked immuno sorbent assay (ELISA). The corresponding kits were used to detect the activity of oxidative stress markers. Compared with nondiabetic eyes, DR mice both at 3 and 6 weeks presented the decreases in the total retinal thickness, the retinal outer nuclear layer (ONL) thickness, and the cells of ganglion cell layer (GCL), with the upregulated CXCL10, pro-inflammatory cytokines and malondialdehyde (MDA), as well as the downregulated levels of superoxide dismutase (SOD), glutathione peroxidase (GPx) and CAT, especially in those at 6 weeks, which were attenuated by the anti-CXCL10 mAb treatment. Moreover, in comparison with the DR mice, mice in the DR + anti-CXCL10 mAb group gained the significant decrease in the number of acellular capillaries of retina, with up-regulations of Claudin-5 and ZO-1 and down-regulations of VEGF and FGF-2. The DR mice injected with anti-CXCL10 mAb demonstrated alleviated retinal pathology as compared to mice at 3 weeks of STZ. Anti-CXCL10 mAb could mitigate the retinal pathology of DR mice, with the decreased inflammation and oxidative stress, thus mediating a delay in the development or disease improvement in patients of DR.