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.

中文翻译：

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Toll 样受体 4 的缺失可改善小鼠糖尿病性视网膜病变

摘要

背景

糖尿病视网膜病变是糖尿病常见的特异性微血管并发症，也是可预防性失明的主要原因。因此，我们的目标是找到一种有前途的糖尿病视网膜病变治疗策略。

方法

为了研究 toll 样受体 4 (TLR4) 在糖尿病性视网膜病变中的作用，我们将链脲佐菌素 (STZ) 注射到野生型 (wt) 和 TLR4 敲除小鼠中以诱导糖尿病。

结果

虽然 STZ 在 wt 和 TLR4 ^-/-小鼠中均诱导了糖尿病，但与糖尿病 wt 小鼠相比，糖尿病小鼠中 TLR4 的缺失显着改善了糖尿病性视网膜病变，这是通过增加的视网膜组织厚度来判断的。此外，TLR4 依赖性 NF-κB 通路、炎性细胞因子释放以及血管内皮生长因子 (VEGF) 和胶质纤维酸性蛋白 (GFAP) 的表达均在注射 STZ 的 wt 小鼠中受到显着刺激，但在 STZ-注射 TLR4 ^-/-小鼠。

结论

TLR4 可作为治疗糖尿病视网膜病变的独立靶点。