Exploring the Mechanisms of the Ferroptosis-Related Gene TGFBR1 in Autoimmune Uveitis Based on Machine Learning...

Autoimmune uveitis (AU) is a group of autoimmune-driven diseases characterized by intraocular inflammation, often leading to severe vision loss. Ferroptosis, a recently discovered form of programmed cell death, has not yet been fully explored in the pathogenesis of AU. This study aims to investigate the role of ferroptosis-related key genes in AU, providing a theoretical foundation for further mechanistic studies. We downloaded GSE198533 data set from the Gene Expression Omnibus (GEO). Through differential gene expression (DEG) analysis, weighted gene coexpression network analysis (WGCNA), and two machine learning models, TGFBR1 and ZFAS1 were identified as critical hub genes. Additionally, we validated the expression of TGFBR1 in retinal inflammation in a mouse model of experimental autoimmune uveitis (EAU) and explored its functional role. The results showed that TGFBR1 expression was significantly downregulated in EAU. Functional experiments demonstrated that TGFBR1 overexpression exacerbated retinal inflammation by promoting lipid peroxidation, downregulating GPX4 and xCT, and altering immune homeostasis by suppressing FOXP3 and enhancing IL-17A expression. Conversely, TGFBR1 inhibition via Galunisertib alleviated retinal inflammation and reversed ferroptosis- and immunity-related protein expression. These findings suggest that TGFBR1 contributes to AU pathogenesis by linking ferroptosis and immune imbalance and may serve as a potential biomarker and therapeutic target, particularly in BD-associated uveitis.