Potential Protective Effect of Empagliflozin on αKlotho/ Autophagy Protein LC3 in Diabetic Retinopathy: Evidence from Diabetic Mice Model

Abstract

Introduction: To study the protective efficacy of Empagliflozin (EMPA), a novel sodium glucose transporter inhibitor antidiabetic drug, on the expression of α-klotho (αKL) protein and of the autophagy key proteins Light chain 3 (LC3) in type 2 diabetic mellitus (T2DM) mice diabetic retinopathy (DR). Materials and Methods: We used the BTBR mouse strain with the ob/ob leptin-deficiency mutation that develops spontaneously severe T2DM, C57/BL mice used as control. EMPA was administrated to the diabetic mice via drinking water for a period of 12 weeks. At the end of the experiment, mice retinas were removed and subjected to further histological analysis: Immunohistochemistry and Immunofluorescence staining for αKL, LC3, protein expression level. Results: Retinal αKL protein expression levels were lower in diabetic mice than control (11.94±4.6 vs 48.4±5.33) % ** P< 0.01), which were restored to near normal with EMPA treatment compared to DM mice (35+20.4% vs 11.94±4.6%,*P<0.05). LC3 levels were increased in diabetic retinas compared to control (29.44±2.84 vs 15.6± 2.23) %, *** P<0.01, and increased with EMPA treatment compared to control (24.77±1.4% vs, 15.6±2.3% *P<0.05). There were no significant changes in ATG5 protein expression in the two groups of diabetic mice with or without EMPA. Conclusions: The data suggested that αKL protein and the autophagy proteins LC3 & ATG5 are involved in the pathogenesis of DR. Our data suggested that αKL and the autophagy key protein LC3 modulators could probably be potential protective factors against retinopathy develops in T2DM patients.