Department of Ophthalmology, Indiana University, Indianapolis, Indiana, USA.
School of Medicine, Indiana University, Indianapolis, Indiana, USA.
BMJ Open Diabetes Res Care. 2022 May;10(3). doi: 10.1136/bmjdrc-2022-002801.
Dapagliflozin, a sodium-glucose transporter inhibitor, effectively reduces blood glucose and is indicated for individuals with kidney diseases and cardiovascular disorders. In this study, we further expand the therapeutic benefit of dapagliflozin in the neural and vascular retina, with the potential to effectively manage diabetic retinopathy (DR), the most common complication of diabetes.
Db/db mice, an animal model of type 2 diabetes, were treated with dapagliflozin orally, and the electroretinogram (ERG) response and acellular capillary numbers were assessed. Messenger RNA levels of inflammatory cytokines were studied using real-time quantitative (q)PCR. We assessed endothelial cell migration in a scratch wound assay and retinal glucose uptake using human retinal endothelial cells.
The dapagliflozin treatment improved the ERG b-wave amplitude and decreased acellular capillary numbers. The scratch wound assay demonstrated a reduction in wound closure after dapagliflozin treatment. Retinal glucose uptake reduced after dapagliflozin treatment compared with the respective controls.
Our studies suggest that dapagliflozin treatment effectively corrects neural and vascular dysfunction of the retina in diabetes. This effect is mediated by a decrease in inflammation and improved glycemic control. In addition, dapagliflozin exhibits decreased wound healing and glucose uptake, which could benefit the retina. Thus, dapagliflozin could be helpful in the management of DR, with multimodal therapeutic effects.
达格列净是一种钠-葡萄糖协同转运蛋白抑制剂，能有效降低血糖，适用于伴有肾脏疾病和心血管疾病的患者。本研究进一步扩展了达格列净在神经和血管视网膜方面的治疗益处，有望有效治疗糖尿病视网膜病变（DR），这是糖尿病最常见的并发症。
采用 db/db 小鼠作为 2 型糖尿病动物模型，给予达格列净口服治疗，评估视网膜电图（ERG）反应和无细胞毛细血管数量。采用实时定量（q）PCR 研究炎症细胞因子的信使 RNA 水平。我们通过划痕实验评估内皮细胞迁移，用人视网膜内皮细胞评估视网膜葡萄糖摄取。
达格列净治疗可改善 ERG b 波振幅，减少无细胞毛细血管数量。划痕实验表明，达格列净治疗后伤口闭合减少。与相应对照组相比，达格列净治疗后视网膜葡萄糖摄取减少。
我们的研究表明，达格列净治疗可有效纠正糖尿病患者的视网膜神经和血管功能障碍。这种作用是通过减少炎症和改善血糖控制来介导的。此外，达格列净表现出降低的伤口愈合和葡萄糖摄取，这可能对视网膜有益。因此，达格列净可能有助于 DR 的管理，具有多模式的治疗效果。
