Employing the Role of SLC40A1-Mediated Microglia Inflammatory Response in Diabetic Retinopathy Based on Single-Cell...

Diabetic retinopathy (DR) is one of the most severe complications of diabetes. Existing treatments are effective but still have many limitations. Thus, it is particularly crucial to uncover novel therapeutic targets and develop more efficacious treatment strategies. In this study, single-cell datasets of retinal and normal retinal tissues of DR patients were obtained from the Gene Expression Omnibus (GEO) database. Using cell annotation, Gene Ontology (GO) pathway enrichment analysis, and cell trajectory analysis, key cell subgroups and their enriched pathways affecting DR progression were selected. DR model mice was constructed. Co-localization between SLC40A1 and microglial cell marker IBA1 was assessed through immunofluorescence detection. qPCR, Western Blot, and ELISA were used to evaluate the expression levels of inflammatory factors. Bioinformatics analysis revealed that in retinal tissues of DR patients, SLC40A1+ microglia exhibited abnormal accumulation and were tightly correlated with inflammatory pathways. Animal experiments showed that the co-localization level of SLC40A1 with IBA1 increased in DR model mice. Further research revealed that knocking out the SLC40A1 gene in microglia can reduce the expression levels of pro-inflammatory factors, including IL-6, TNF-α, and IL-1β. It effectively alleviated the pathologic characteristics of DR. SLC40A1+ microglia modulated inflammatory responses to control DR progression, offering promising avenues for new therapeutic targets in DR treatment.