The role and mechanism of the miR-137 regulatory axis in diabetic retinopathy.

BACKGROUND

Diabetic retinopathy (DR) is a leading cause of blindness, yet its molecular mechanisms are incompletely understood. This study aimed to investigate the role and regulatory mechanism of miR-137 in DR.

METHODS

A total of 176 participants were enrolled in this study, comprising 126 patients with DR and 50 healthy controls. According to standard criteria, the DR patients were categorized into non-proliferative (NPDR, n = 111) and proliferative (PDR, n = 15) groups. Clinical parameters and serum miR-137 expression levels were measured in all subjects. In vitro, a high-glucose (HG) model was established using HRCECs. Transfection, inhibitor treatments, and target validation (dual-luciferase assay, rescue experiments) were employed to assess miR-137's role in oxidative stress, ferroptosis, inflammation, and its target gene Integrin α5 (ITGA5).

RESULTS

Clinically, serum miR-137 was significantly downregulated in DR patients (0.65 ± 0.05 vs. 0.99 ± 0.10, p < 0.001), negatively correlating with HbA1c, FBG, and LogMAR scores, and identified as a factor associated with proliferative DR progression. In vitro, HG suppressed miR-137 via ferroptosis, while miR-137 overexpression alleviated HG-induced oxidative stress, ferroptosis, and inflammation. ITGA5 was confirmed as a direct target of miR-137, and its overexpression reversed the protective effects of miR-137 mimic.

CONCLUSION

This study reveals that miR-137 exerts a protective role in DR. Its downregulation disinhibits ITGA5, driving oxidative stress, ferroptosis, and inflammation, thereby exacerbating retinal microvascular damage.