June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Induction of Epithelial-Mesenchymal Transition by SGLT2 reduction in diabetic cataract development and progression via dapagliflozin nanoparticles
Author Affiliations & Notes
  • Pei-Wen Cheng
    Medical Education and Research, Kaohsiung Veterans General Hospital, Taiwan
  • Ying-Ying Chen
    Department of Ophthalmology, Kaohsiung Veterans General Hospital, Taiwan
  • Footnotes
    Commercial Relationships   Pei-Wen Cheng None; Ying-Ying Chen None
  • Footnotes
    Support  No
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 1223. doi:
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      Pei-Wen Cheng, Ying-Ying Chen; Induction of Epithelial-Mesenchymal Transition by SGLT2 reduction in diabetic cataract development and progression via dapagliflozin nanoparticles. Invest. Ophthalmol. Vis. Sci. 2023;64(8):1223.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : The sodium glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Dapa) can be used to treat diabetes. Chronic hyperglycemia triggers the overproduction of AKR1B1 and receptor for advanced glycation end product (RAGE), which causes epithelial-mesenchymal transition (EMT) formation in the lens epithelial cells of diabetic cataracts, but it is unclear whether EMT formation in LECs is related to an abnormal rise in SGLT2. The nano eye drops are an ophthalmic treatment with improved potency and reduced side effects. Here we examine how Dapa or nano eye-drops (DapaN) reduce EMT formation in LECs of diabetes mellitus (DM) cataracts.

Methods : SD rats were injected with STZ (65 mg/kg, ip) and provided with 10 % glucose solution for the next 24 h to prevent hypoglycaemia. Immunofluorescence Staining were used to quantify protein levels including RAGE, SGLT2, N-cadherin and E-cadherin in the rat lens epithelial cell. All data were expressed as the mean ± SEM (n=12 for each group). Mann-Whitney U and Chi-square tests were employed to compare the group differences.

Results : The present study investigated the therapeutic activity of Dapa, constructed from polyvinylpyrrolidone (PVP) and HPBCD, in the treatment of DM cataracts using nanotechnology-based delivery systems. According to our findings, targeting EMT biomarkers with nano-Dapa drops (0.456 mg/10 ml/eye) or oral Dapa (1.2 mg/kg/day) inhibited SGLT2 and inhibited AKR1B1 overexpression and decreased AcSOD2- and RAGE-induced EMT in diabetic cataracts. Additionally, our findings suggest that nanotechnology-based Dapa eye drops (Dapa-PVP-HPBCD) can effectively improve the solubility of Dapa in aqueous solution. The results suggest that Dapa can effectively decrease SGLT2 activation and inhibit AcSOD2- and RAGE-induced EMT in the LECs of diabetic cataracts, a powerful tool for prevention of cataract pathogenesis in DM patients.

Conclusions : Taken together, results suggest that the SGLT2-mediated DM cataract therapy may involve the AKR1B1-RAGE-AcSOD2-EMT pathway. DM patients may benefit from nano eye drops (DapaN) and Dapa for the pharmacological prevention of cataracts. Consequently, nano-Dapa drop supplementation offers immense potential for treating diabetic cataracts.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

 

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