IMR Press / FBL / Volume 27 / Issue 12 / DOI: 10.31083/j.fbl2712321
Open Access Original Research
Determining the Role of SGLT2 Inhibition with Dapagliflozin in the Development of Diabetic Retinopathy
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1 Dobney Hypertension Centre, School of Biomedical Science – Royal Perth Hospital Unit, University of Western Australia, 6009 Crawley, WA, Australia
2 Department of Molecular Ophthalmology, University of Western Australia, 6009 Crawley, WA, Australia
3 Dobney Hypertension Centre, School of Medicine – Royal Perth Hospital Unit, University of Western Australia, 6009 Crawley, WA, Australia
4 Department of Cardiology, Royal Perth Hospital, 6000 Perth, WA, Australia
5 Department of Nephrology, Royal Perth Hospital, 6000 Perth, WA, Australia
*Correspondence: (Lakshini Y. Herat)
These authors contributed equally.
These authors contributed equally.
Academic Editor: Riccardo Nevola
Front. Biosci. (Landmark Ed) 2022, 27(12), 321;
Submitted: 22 July 2022 | Revised: 14 November 2022 | Accepted: 22 November 2022 | Published: 12 December 2022
(This article belongs to the Special Issue An Update on Sodium Glucose Co-Transporters)
Copyright: © 2022 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.

Background: Diabetic retinopathy (DR) is a major cause of blindness globally. Sodium Glucose Cotransporter-2 (SGLT2) inhibitors have been demonstrated to exert cardiorenal protection in patients with diabetes. However, their potential beneficial effect on DR is less well studied. The aim of the present study was to determine the effects of the SGLT2 inhibition with Dapagliflozin (DAPA) on DR in well-characterised DR mouse models and controls. Methods: Dapagliflozin was administered to mice with and without diabetes for 8 weeks via their drinking water at 25 mg/kg/day. Urine glucose levels were measured weekly and their response to glucose was tested at week 7. After 8 weeks of treatment, eye tissue was harvested under terminal anaesthesia. The retinal vasculature and neural structure were assessed using immunofluorescence, immunohistochemistry and electron microscopy techniques. Results: Dapagliflozin treated DR mice exhibited metabolic benefits reflected by healthy body weight gain and pronounced glucose tolerance. Dapagliflozin reduced the development of retinal microvascular and neural abnormalities, increased the beneficial growth factor FGF21 (Fibroblast Growth Factor 21). We highlight for the first time that SGLT2 inhibition results in the upregulation of SGLT1 protein in the retina and that SGLT1 is significantly increased in the diabetic retina. Conclusions: Blockade of SGLT2 activity with DAPA may reduce retinal microvascular lesions in our novel DR mouse model. In conclusion, our data demonstrates the exciting future potential of SGLT1 and/or SGLT2 inhibition as a therapeutic for DR.

diabetic retinopathy
mouse models
sodium glucose cotransporters
SGLT2 inhibitors
retinal vasculature
VM2018/Royal Perth Hospital- Research Foundation WA
Y20G-MATV/Diabetes Australia Research Program
DRWA-LHerat-2020/Diabetes Research WA
Raine-LHerat-2020/Raine Medical Research Foundation, WA
Fig. 1.
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