SGLT2 inhibition with empagliflozin attenuates retinal oxidative stress and damage in diabetic mice

To investigate the effects of empagliflozin (EMPA), an SGLT2 inhibitor, on retinal damage in diabetic mice, exploring its potential as a therapeutic strategy for diabetic retinopathy (DR). DR was induced by a high-fat diet and streptozotocin injections, followed by EMPA treatment. The study employed multiple detection methods, including assessments of hyperglycemia levels, detection of retinal oxidative stress markers, mitochondrial-associated alterations (TOM20 expression), histological examination of retinal tissue, electroretinography for evaluating retinal function, and the expression of structural or junction-associated proteins, including ZO-1, occludin, and vimentin. EMPA treatment exerted significant beneficial effects on diabetic mice with retinopathy. It notably alleviated hyperglycemia, reduced retinal oxidative stress (as demonstrated by decreased ROS production and increased levels of antioxidant proteins HO-1 and NRF2), and partially normalized TOM20 expression. Histological analysis revealed that EMPA mitigated retinal thinning, reduced retinal cell apoptosis, and attenuated gliosis. Electroretinography results showed that EMPA improved retinal function by preserving the amplitudes of a-waves and b-waves. Additionally, EMPA increased the expression of retinal structural or junction-associated proteins. In conclusion, EMPA treatment was associated with attenuation of retinal injury in diabetic mice, along with improvements in systemic glucose levels, oxidative stress markers, and retinal structure and function. However, as EMPA also reduced blood glucose levels, it remains unclear whether these retinal effects are independent of glycemic control. These findings support further investigation into the potential role of EMPA in early diabetic retinal injury.