Diabetes initiates inflammation that can impair the retinal vasculature, and lead to diabetic retinopathy; one of the leading causes of blindness. Inflammatory pathways have been examined as potential therapeutic targets for diabetic retinopathy, but there is still a need for early-stage treatments. We hypothesized that the CD40-TNF Receptor Associated Factor 6 (TRAF6) axis plays a pivotal role in the onset of diabetic retinopathy, and that the CD40-TRAF6 axis would be a prime therapeutic target for early-stage non-proliferative diabetic retinopathy. The CD40-TRAF6 complex can initiate NFκB activation, inflammation, and tissue damage. Further, CD40 and TRAF6 are constitutively expressed on Muller glia, and upregulated in the diabetic retina. Yet the role of the CD40-TRAF6 complex in the onset of diabetic retinopathy is still unclear. In the current study, we examined the CD40-TRAF6 axis in diabetic retinopathy using a small molecule inhibitor (SMI-6877002) on streptozotocin-induced diabetic mice. When CD40-TRAF6-dependent inflammation was inhibited, retinal vascular leakage and capillary degeneration was ameliorated in diabetic mice. Collectively, these data suggest that the CD40-TRAF6 axis plays a pivotal role in the onset of diabetic retinopathy, and could be a novel therapeutic target for early diabetic retinopathy.

糖尿病引发的炎症会损害视网膜血管系统，并导致糖尿病性视网膜病变；失明的主要原因之一。炎症通路已被检查为糖尿病视网膜病变的潜在治疗靶点，但仍需要早期治疗。我们假设 CD40-TNF 受体相关因子 6 (TRAF6) 轴在糖尿病视网膜病变的发生中起关键作用，并且 CD40-TRAF6 轴将成为早期非增殖性糖尿病视网膜病变的主要治疗靶点。CD40-TRAF6 复合物可以启动 NFκB 激活、炎症和组织损伤。此外，CD40 和 TRAF6 在 Muller 胶质细胞上组成型表达，并在糖尿病视网膜中上调。然而，CD40-TRAF6 复合物在糖尿病视网膜病变发作中的作用仍不清楚。在当前的研究中，我们使用小分子抑制剂 (SMI-6877002) 在链脲佐菌素诱导的糖尿病小鼠身上检查了糖尿病视网膜病变中的 CD40-TRAF6 轴。当 CD40-TRAF6 依赖性炎症受到抑制时，糖尿病小鼠的视网膜血管渗漏和毛细血管变性得到改善。总的来说，这些数据表明 CD40-TRAF6 轴在糖尿病视网膜病变的发生中起着关键作用，并可能成为早期糖尿病视网膜病变的新治疗靶点。