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Updated: May 11, 2026
Retinal Explant of the Adult Mouse Retina as an Ex Vivo Model for Studying Retinal Neurovascular Diseases
Published on: December 9, 2022
MSC-derived exosomal miR-125b-5p suppressed retinal microvascular endothelial cell ferroptosis in diabetic
Jun Tong1,2, Yueqin Chen1, Xinru Ling1
1Department of Ophthalmology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu Province 210008, People's Republic of China.
Abstract:
Progressive endothelial cell injury of retinal vascular is a vital factor in diabetic retinopathy (DR) pathogenesis. Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) showed beneficial effects on DR. However, the effects of MSC-sEVs on endothelial dysfunction of DR and the mechanism is still unclear. In this study, MSC-sEVs mitigated retinal blood-retina barrier (BRB) impairment in rats with streptozotocin (STZ)-induced DR by reducing ferroptosis in vivo and in vitro. MSC-sEVs miRNA sequencing analysis revealed that miR-125b-5p may mediate human retina microvascular endothelial cells (HRMECs) ferroptosis and P53 as a downstream target based on dual-luciferase reporter assays. Silencing miR-125b-5p in MSC-sEVs reversed the therapeutic effects of MSC-sEVs on rats with DR and advanced glycation end products (AGEs)-treated HRMECs. Additionally, overexpression of miR-125b-5p could diminish ferroptosis in HRMECs, and this effect could be effectively reversed by overexpressing P53. This study indicated the potential therapeutic effect of MSC-sEVs on vascular endothelial function maintenance and that the delivery of sEVs carrying miR-125b-5p could prevent endothelial cell ferroptosis by inhibiting P53, thereby protecting the BRB.
Insights
Mesenchymal stem cell-derived extracellular vesicles (MSC-sEVs) protect the retina in diabetic retinopathy (DR) by reducing cell death. They deliver miR-125b-5p, which inhibits P53, preserving the blood-retina barrier (BRB).
Area of Science:
- Ophthalmology and Visual Sciences
- Regenerative Medicine
- Cell Biology
Background:
- Diabetic retinopathy (DR) involves progressive retinal vascular endothelial cell injury.
- Mesenchymal stem cells-derived small extracellular vesicles (MSC-sEVs) show therapeutic potential for DR.
- The precise mechanisms by which MSC-sEVs improve endothelial dysfunction in DR remain unclear.
Purpose of the Study:
- To investigate the effects of MSC-sEVs on endothelial dysfunction in diabetic retinopathy (DR).
- To elucidate the underlying molecular mechanisms, particularly involving ferroptosis and specific microRNAs.
- To evaluate the therapeutic potential of MSC-sEVs in maintaining retinal blood-retina barrier (BRB) integrity.
Main Methods:
- Utilized a rat model of streptozotocin (STZ)-induced diabetic retinopathy (DR).
- Assessed the impact of MSC-sEVs on retinal blood-retina barrier (BRB) integrity and ferroptosis in vivo and in vitro.
- Performed miRNA sequencing on MSC-sEVs and employed dual-luciferase reporter assays to identify miR-125b-5p and its target P53.
- Investigated the effects of silencing or overexpressing miR-125b-5p and P53 in human retina microvascular endothelial cells (HRMECs) and STZ-induced DR rats.
Main Results:
- MSC-sEVs significantly mitigated BRB impairment in STZ-induced DR rats by reducing ferroptosis.
- MiRNA sequencing identified miR-125b-5p within MSC-sEVs, which targets P53 and mediates ferroptosis in HRMECs.
- Silencing miR-125b-5p in MSC-sEVs reversed their therapeutic effects on DR rats and AGEs-treated HRMECs.
- Overexpression of miR-125b-5p reduced ferroptosis in HRMECs, an effect counteracted by P53 overexpression.
Conclusions:
- MSC-sEVs hold therapeutic promise for maintaining vascular endothelial function in diabetic retinopathy (DR).
- MSC-sEVs deliver miR-125b-5p, which inhibits P53, thereby preventing endothelial cell ferroptosis and protecting the BRB.
- Targeted delivery of miR-125b-5p via sEVs represents a potential strategy for treating DR-associated vascular complications.
