Single-cell transcriptomic analysis of ferroptosis-associated cell populations in the progression of diabetic retinopathy.

BACKGROUND

Diabetic retinopathy (DR), a common microvascular complication of diabetes mellitus, has been associated with ferroptosis-related pathological mechanisms. Evidence indicates that ferroptosis may contribute to retinal injury and disease progression. The present analysis aimed to characterize ferroptosis-associated cell subsets and their roles in the progression of DR.

METHOD: Single-cell RNA sequencing data derived from diabetic rat models of DR were obtained from the Gene Expression Omnibus database. A total of 464 ferroptosis-related genes were used to calculate ferroptosis scores. Data processing and analysis were performed using the Seurat R package, with differentially expressed genes identified via the FindAllMarkers function. Functional enrichment analyses were conducted using the clusterProfiler package. Protein-protein interaction networks were constructed using the STRING database, and intercellular communication was predicted using CellChat. Key findings were validated through reverse transcription quantitative polymerase chain reaction (RT-qPCR).

RESULTS

Cell clustering identified nine principal retinal cell types. Compared with normal control groups, the DR group demonstrated altered proportions of Müller cells, vascular endothelial cells, microglia, and cone photoreceptor cells. Ferroptosis-score-related differences were most evident in Müller cells and rod cells. In the revised WT-baseline sensitivity analysis, the high-ratio ferroptosis-score cell distribution remained significantly altered in Rod and Müller cells after multiple-testing correction.

CONCLUSION

This study identified key ferroptosis-associated retinal cell populations, with an emphasis on the functional roles of ferroptosis-associated Müller cell subsets in the context of DR. These findings provide further insight into the cellular mechanisms underlying DR and highlight potential molecular targets for therapeutic intervention.