Potential Ferroptosis-Related Genes and Immune Infiltration in Form-Deprivation Myopia: An Integrative Bioinformatics...

Area of Science:

• Ophthalmology
• Genetics
• Cell Biology

Background:

• Form-deprivation myopia (FDM) is a significant visual impairment with complex molecular underpinnings.
• Understanding the genetic and cellular mechanisms of FDM is crucial for developing effective interventions.
• Ferroptosis, a regulated form of cell death, and immune responses are increasingly implicated in ocular diseases.

Purpose of the Study:

• To explore the molecular mechanisms of FDM by identifying ferroptosis-related genes (FRGs).
• To characterize the immune infiltration landscape in FDM.
• To identify potential diagnostic and therapeutic targets for FDM.

Main Methods:

• Transcriptomic data analysis (GSE223434, GSE210238) to identify differentially expressed FRGs (FRDEGs).
• Weighted gene co-expression network analysis (WGCNA) and machine learning (LASSO, Random Forest) for hub gene screening.
• Immune infiltration analysis using CIBERSORT and in vitro validation with TGF-β2-induced human scleral fibroblasts (HSFs).

Main Results:

• 256 FRDEGs were identified; PRKAA1, TGFB3, and WWTR1 were selected as hub genes with diagnostic potential (AUCs 0.725–0.762).
• Significant differences in monocyte infiltration were observed in FDM retinas.
• In vitro assays confirmed TGF-β2 upregulated hub genes, reduced GPX4, and induced ferroptosis, effects reversed by ferrostatin-1 (Fer-1). Silencing hub genes promoted ferroptosis and fibrotic markers, rescued by Fer-1.

Conclusions:

• A ferroptosis-immune axis involving PRKAA1, TGFB3, and WWTR1 may contribute to myopia pathogenesis.
• These hub genes are promising candidates for diagnostic markers in FDM.
• The findings offer a preliminary biological perspective on myopic scleral remodeling regulated by ferroptosis.