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. 2025 Jun;62(6):831-844.
doi: 10.1007/s00592-024-02400-3. Epub 2024 Nov 7.

Mir-509-3p targets SLC25A13 to regulate ferroptosis and protect retinal endothelial cells in diabetic retinopathy

Meiqing Ren  1 , Qian Xu  1 , Jie Luan  1 , Yan Ni  1 , Bo Xie  2
Affiliations

Mir-509-3p targets SLC25A13 to regulate ferroptosis and protect retinal endothelial cells in diabetic retinopathy

Meiqing Ren et al. Acta Diabetol. 2025 Jun.

Abstract

Aims: Diabetic retinopathy (DR) is a major complication of diabetes that leads to vision impairment. The aim of this study was to investigate the regulatory role of miR-509-3p in DR, focusing on its interaction with SLC25A13 and its impact on retinal endothelial cell function, oxidative stress, apoptosis, and ferroptosis.

Methods: HRVECs were cultured in high-glucose (HG) conditions to establish an in vitro DR model. miR-509-3p mimics and inhibitors were transfected into HRVECs to assess their effects on SLC25A13 expression, cell viability, apoptosis, reactive oxygen species (ROS) levels, and ferroptosis markers. A luciferase reporter assay and RNA immunoprecipitation were used to confirm the binding of miR-509-3p to SLC25A13 mRNA. For in vivo validation, agomiR-509-3p was injected into the vitreous of DR mice, and retinal thickness, pathological damage, and apoptosis were evaluated. Ferroptosis-related markers (GPX4, TlR4, ASCL4) were analyzed in HRVECs to explore the mechanism of miR-509-3p in regulating ferroptosis.

Results: In vitro, miR-509-3p significantly decreased SLC25A13 expression, resulting in enhanced HRVEC viability, reduced apoptosis, and lower ROS levels under HG conditions. Overexpression of SLC25A13 reversed these protective effects, while miR-509-3p knockdown exacerbated oxidative stress and apoptosis. In vivo, agomiR-509-3p increased retinal thickness, reduced pathological damage, and decreased apoptosis in DR mice. Ferroptosis marker analysis revealed that miR-509-3p upregulated GPX4 expression and downregulated TlR4 and ASCL4, whereas SLC25A13 overexpression reversed these effects, further linking miR-509-3p to the regulation of ferroptosis.

Conclusions: miR-509-3p exerts a protective effect in DR by targeting SLC25A13, reducing oxidative stress, apoptosis, and ferroptosis in retinal endothelial cells. These findings highlight the potential of miR-509-3p as a therapeutic target for DR management.

Keywords: Diabetic retinopathy; HRVECs; MiR-509-3p; SLC25A13.

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Conflict of interest statement

Declarations. Conflict of interest: The authors of the research affirm that they had no commercial or financial relationships that could increase the likelihood of a conflict of interest. Ethical approval: All animal studies have been approved by the Ethics Committee of Zhongda hospital Southeast University (ID: 20240206001) and performed in accordance with the ethical standards.

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