Clinical evidence-based investigation of developmental mechanism in diabetic retinopathy

前瞻性随机临床试验显示，非诺贝特是PPARpha的一种药物，在抑制糖尿病视网膜病变的发展或进展方面有效。在这方面，我们研究了PPARα刺激的血管内皮细胞的基因表达和表观基因组图谱。在血管细胞基因表达谱中，PPARpha的刺激具有抗炎和抗血栓作用。表观组学分析表明，血栓调节蛋白直接受PPARpha转录调控，并介导炎症和促血栓形成基因的这种基因调控。这些发现表明，血栓调节蛋白是糖尿病视网膜病变血管防御机制的关键调节因子，可应用于未来的治疗策略。

Prospective-randomized clinical trials revealed efficacy of fenofibrate, a PPARalpha gonist, in inhibition of diabetic retinopathy development or progression. In this regard, we investigated gene expression and epigenomic profile of PPARalpha - stimulated vascular endothelial cells. Stimulation of PPARalpha showed anti-inflammatory and anti-thrombotic effects in gene expression profile in vascular cells. Epigenomic analyses revealed thrombomodulin is regulated directly under transcriptional regulation of PPARalpha and mediate such gene regulation of inflammatory and pro-thrombotic genes. These findings suggest that thrombomodulin is a key regulator of vascular defense mechanism in diabetic retinopathy and could be applied to future treatment strategies.