Abstract
Purpose :
Metabolic disease is complicated and metabolic-related complications have crucial role in growth rate of cataract. Lens` opacity and oxidation, advanced glycation end products (AGEs) formation, and sorbitol accumulation through aldose reductase (AR) conversion of glucose have been linked to distinctive rise in blood glucose and lens` protein glycosylation during cataract development. At present, there is no clear evidence for anti-diabetic drug being linked to lowered cataract risks. Therefore, finding effective method to treat diabetic cataract or delay cataract formation is necessary. Sodium glucose cotransporter 2 (SGLT2) inhibitor, also known as dapagliflozin (Dapa) can be used to treat diabetes. Here, we examined how Dapa reduce EMT in LECs of DM cataracts.
Methods :
Fluorescence was used to estimate the AKR1B1, RAGE, SGLT2/GLUT1 and EMT biomarkers in the human lens epithelial sections from DM, non-DM cataracts and DM cataract rats. Besides, SD rats were injected with streptozocin (STZ) (65 mg/kg, ip), Dapa (1.2 mg/kg/day) treatment for 6-12 weeks.
Results :
In this study, Immunofluorescent staining demonstrated that IGFBP2, GTP-Rac1, SGLT2 and FBN1 were significantly enhanced in the human lens epithelial sections from DM (+) than DM (-) cataract patients. Besides, SGLT2, RAGE, IGFBP2, GTP-Rac1, myosin IIB and FBN1 were also significantly enhanced in LECs of the DM cataract rats. Interestingly, treatment with the Dapa delayed the onset and progression of cataract in DM cataract rats, and abolished SGLT2-induced IGFBP2-RAGE-Rac1-GTP-myosin II B and FBN1 production, which decreased EMT formation in LECs of DM cataracts.
Conclusions :
Taken together, these results suggest that SGLT2-mediated cataract therapy may involve the RAC1-GTP-myosin II B and FBN1-EMT pathways. DM patients may benefit from Dapa for the pharmacological prevention of cataracts. Consequently, Dapa supplementation offers immense potential for treating diabetic cataract
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.