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

Authors: Nakhoul N , Ertracht O , Igbariye A , Gehard H , Mann I , Tadmor H , Saed R , Nakhoul F* and Atar S

DOI: 10.23880/doij-16000S1-007

Special Issue 1: Diabetes and Eye Complications

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) % * < 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.

Keywords: Diabetic mice; Diabetic retinopathy; Nephropathy; Empagliflozin; αKlotho; LC3; Ganglion cell layer

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