Abstract
Purpose :
Diabetic retinopathy (DR) is a chronic and progressive complication of diabetes. Dapagliflozin, a new class of anti-diabetic medication, is beneficial in reducing blood glucose; however, its role in DR remains unknown. Therefore, this study aims to investigate the protective effect of dapagliflozin on the development of DR.
Methods :
The db/db mice were treated with dapagliflozin via diet for six months and the body weight, food consumption monitored every week. The blood glucose, HbA1c and electroretinogram (ERG) were assessed at 2 and 6 months. At study termination, the retinas were processed for trypsin digestions and real-time qPCR. In parallel, the human retinal endothelial cells (HRECs) were treated with dapagliflozin concentrations 0.1-100 uM in a logarithmic range. The cell viability was assessed using Alamar Blue Assay, and the migration response was studied using a scratch wound-healing assay.
Results :
The dapagliflozin treatment reduced blood glucose and HbA1C; however, there was no change in body weight or food intake. The db/db mice exhibited higher amplitude for ERG ‘b’ wave, which was decreased after dapagliflozin treatment. Dapagliflozin treatment resulted in downregulation of mRNA for pro-inflammatory markers along with a decrease in acellular capillary numbers in db/db mice. The HRECs were viable at all concentrations except for the 100 μM dapagliflozin dose. The scratch wound assay demonstrated a significant reduction in wound closure and rate of migration after 4 and 8 hours of dapagliflozin treatment for the 50 and 100 μM concentrations.
Conclusions :
Overall, dapagliflozin treatment was successful in regulating photopic ERG ‘b’ wave amplitude, glycemic control and, decreasing acellular capillary numbers and inflammation in vivo, and decreasing the wound closure in in vitro assays. In conclusion, our studies suggest that dapagliflozin could be beneficial in the treatment of DR due to its effect on glycemic control and potential anti-inflammatory and anti-angiogenic action.
This is a 2021 ARVO Annual Meeting abstract.