Background: Diabetic retinopathy (DR) remains a leading cause of vision impairment globally, particularly in urbanizing regions. This study integrates epidemiological data from the Beichen Eye Study in Tianjin, China, with recent molecular findings to provide a comprehensive understanding of DR progression, with a focus on ferroptosis and adiponectin-related pathways.

Methods: A population-based, cross-sectional survey was conducted among individuals aged ≥50 in the Beichen district. Participants underwent clinical evaluations including fundus photography and OCT to assess the prevalence and severity of DR and diabetic macular edema (DME). Concurrently, laboratory studies investigated the role of ferroptosis and adiponectin signaling in DR pathogenesis using diabetic mouse models, cultured human retinal microvascular endothelial cells (HRMECs), and patient-derived samples.

Results: Among 5,648 participants, 1,182 had diabetes, with DR prevalence recorded at 28.8% and DME at 14.13%. Risk factor analysis revealed significant correlations with blood glucose levels and diabetes duration. Molecular investigations indicated elevated markers of ferroptosis—such as lipid peroxidation, reactive oxygen species, and iron accumulation—in HRMECs and diabetic retinal tissue. Inhibiting ferroptosis via Fer-1 markedly reduced microvascular damage in diabetic mice. Additionally, adiponectin expression was found to decline with DR progression. Single-cell RNA sequencing, ELISA assays, and hub gene analysis highlighted the central role of the ADIPOQ gene and its regulation of the AGEs-RAGE signaling axis in exacerbating DR.

Conclusion: This integrated approach underscores a high prevalence of DR and DME in the Beichen region and identifies ferroptosis and adiponectin-mediated pathways as critical contributors to DR pathogenesis. These findings support the potential of targeted molecular therapies, alongside glycemic control, to mitigate the burden of diabetic retinal disease.