Crosstalk between TRPV1 and immune regulation in Fuchs endothelial corneal dystrophy

• Published in: Clinical immunology (Orlando, Fla.) Fla.), 2023-09, Vol.254, p.109701-109701, Article 109701
• Main Authors: Cai, Yuchen, Chen, Jin, Sun, Hao, Zhou, Tianyi, Cai, Xueyao, Fu, Yao
• Format: Article
• Language: English
• Subjects: Fuchs endothelial corneal dystrophy; Gene therapy; Immune landscape; Regulatory T cell; Transient receptor potential vanilloid 1
• ISSN: 1521-6616; 1521-7035
• DOI: 10.1016/j.clim.2023.109701

Fuchs endothelial corneal dystrophy (FECD) is the leading indication for corneal transplantation worldwide. Our aim was to investigate the role of transient receptor potential vanilloid subtype 1 (TRPV1) and the associated immune regulation contributing to this pathological condition. Significant upregulation of TRPV1 was detected in the H2O2-induced in vitro FECD model. Based on gene expression microarray dataset GSE142538 and in vitro results, a comprehensive immune landscape was studied and a negative correlation was found between TRPV1 with different immune cells, especially regulatory T cells (Tregs). Functional analyses of the 313 TRPV1-related differentially expressed genes (DEGs) revealed the involvement of TRP-regulated calcium transport, as well as inflammatory and immune pathways. Four TRPV1-related core genes (MAPK14, GNB1, GNAQ, and ARRB2) were screened, validated by microarray dataset GSE112039 and the combined validation dataset E-GEAD-399 & 564, and verified by in vitro experiments. Our study suggested a potential crosstalk between TRPV1 and immune regulation contributing to FECD pathogenesis. The identified pivotal biomarkers and immune-related pathways provide a novel framework for future mechanistic and therapeutic studies of FECD.