Abstract: PO0716
Empagliflozin (SGLT-2 Inhibitor) Ameliorates Early Features of Diabetic Retinopathy and Nephropathy in Type 2 Diabetic Mice Model via the Klotho Protein
Session Information
- Diabetic Kidney Disease: Basic - II
November 04, 2021 | Location: On-Demand, Virtual Only
Abstract Time: 10:00 AM - 12:00 PM
Category: Diabetic Kidney Disease
- 601 Diabetic Kidney Disease: Basic
Authors
- Nakhoul, Farid M., Research Institute Galilee Medical Center, Nahariya, Israel
- Ertracht, Offir, Research Institute Galilee Medical Center, Nahariya, Israel
- Nakhoul, Nakhoul, Ophtalmology Division Baruch Padeh Poriya Medical Center, Tiberias, Israel
- Farber, Evgeny, Diabetes Research Lab. Baruch Padeh Poriya Medical Center, Tiberias, Israel
- Tadmor, Hagar, Diabetes Research Lab. Baruch Padeh Poriya Medical Center, Tiberias, Israel
- Saad, Ranin, Diabetes Research Lab. Baruch Padeh Poriya Medical Center, Tiberias, Israel
- Atar, Shaul, Research Institute Galilee Medical Center, Nahariya, Israel
- Igbariye, Anas, Research Institute Galilee Medical Center, Nahariya, Israel
Background
The diabetic nephropathy (DN) and diabetic retinopathy (DR) are the most common serious vascular complications of diabetes Chronic hyperglycemia in DM triggers different processes that leads to Diabetic Retinopathy (DR) and Nephropathy (DN) development. α-Klotho (KL) is an anti-aging gene encoding a protein with multiple pleiotropic effects, involved in suppression oxidative stress and inflammation processes. We investigate the protective effect of Empagliflozin (EMPA) on the expression of KL on DN &DR in DM mice model.
Methods
BTBR mice with ob/ob leptin-deficiency develops severe type II DM with DN and DR. 8 weeks-old male mice were randomly divided into 3 groups: C57BL/6J Wild Type, BTBR ob/ob vehicle and BTBR ob/ob treated with EMPA. Mice were sacrificed after 13 weeks of treatment. Mice retinas were removed and fixed by immersion in 2% paraformaldehyde overnight at 4°C. After PBS rinses eyes were immersed in increased concentrations of sucrose-PBS solutions at 4°C and finally frozen in O.C.T. Cryostat sections (16 µm) were incubated overnight at 4°C with primary anti-KL antibody, then for 1 h with secondary antibody. We assessed immunohisto-fluorescence intensity of each experimental group, using an Olympus BX53 fluorescent microscope, and identical exposure for each image. Finally, the data is presented as percent area of the inner plexiform layer (IPL), especially the ganglionic cells, covered with positive signal to KL. Concomitantly, kidneys were removed and subjected to similar immunostaining for the KL protein.
Results
KL expression in the IPL (ganglionic cells) was 48.3±2.7 % in control mice, 11.9±2.% in DM mice (P<0.001 vs. control) and 20.4±2.% in DM mice treated with EMPA (P<0.05 vs. un treated DM mice). In control mice KL expression was 6.8% of the renal tissue area, expression was attenuated in the DM mice occupying 0.065 %, in DM mice treated with EMPA, the KL expression reached 4%.
Conclusion
The data suggested that KL protein can play a potential protective factor against retinopathy and nephropathy in DM mice. Early therapy with EMPA that targets the early pathogenesis of DR and DN, is wildly needed to prevent the onset & slow the progression of those pathologies to to vision loss and dialysis, respectively.