Abstract
Fuchs' endothelial corneal dystrophy (FECD) is a genetic eye disorder that often requires corneal transplantation and lacks targeted therapies. This study aimed to identify new biomarkers and mechanisms of FECD progression. We integrated three GEO corneal endothelial datasets to find consistently differentially expressed genes (DEGs) and constructed a protein-protein interaction (PPI) network to identify hub genes. The identified genes were validated using single-cell RNA sequencing (scRNA-seq) in a rat endothelial injury and endothelial-to-mesenchymal transition (EndMT) model. A competing endogenous RNA (ceRNA) network was predicted using multiple bioinformatics databases. Among 24 common DEGs, Secreted Phosphoprotein 1 (SPP1) was identified as a consistently top-ranked upregulated hub gene. This upregulation was validated in an independent dataset (AUC = 0.833) and aligned with the EndMT phase in our model. We propose that SPP1 is a potential biomarker and therapeutic target for FECD, and the NEAT1/miR-181b-5p/SPP1 axis might be a regulatory RNA pathway involved in FECD development.