Deletion of toll-like receptor 4 ameliorates diabetic retinopathy in mice

Abstract

Background Diabetic retinopathy is a common and specific microvascular complication of diabetes, which is also the leading cause of preventable blindness. Therefore, we aimed to find a promising therapeutic strategy for diabetic retinopathy. Methods To investigate the role of toll-like receptor 4 (TLR4) in the diabetic retinopathy, we injected streptozotocin (STZ) into wild-type (wt) and TLR4 knock-out mice to induce diabetes. Results While STZ induced diabetes both in wt and TLR4−/− mice, deletion of TLR4 in diabetic mice significantly improved diabetic retinopathy compared to diabetic wt mice, as judged by the enhanced thickness of retinal tissue. Furthermore, TLR4-dependent NF-κB pathway, inflammatory cytokine release and the expressions of vascular endothelial growth factor (VEGF) and glial fibrillary acidic protein (GFAP), which were all remarkably stimulated in STZ-injected wt mice, were inhibited in STZ-injected TLR4−/− mice. Conclusion TLR4 could serve as an independent target for treating diabetic retinopathy.