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Published on: November 22, 2024
Crosstalk between TRPV1 and immune regulation in Fuchs endothelial corneal dystrophy
Yuchen Cai1, Jin Chen1, Hao Sun1
1Department of Ophthalmology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Orbital Diseases and Ocular Oncology, Shanghai, China.
Insights
Fuchs endothelial corneal dystrophy (FECD) involves Transient Receptor Potential Vanilloid 1 (TRPV1) and immune cells. This study identifies TRPV1-related genes and pathways, suggesting a new therapeutic target for FECD.
Area of Science:
- Ophthalmology
- Immunology
- Molecular Biology
Background:
- Fuchs endothelial corneal dystrophy (FECD) is a primary cause of corneal transplantation globally.
- The role of Transient Receptor Potential Vanilloid subtype 1 (TRPV1) and immune regulation in FECD pathogenesis remains unclear.
Purpose of the Study:
- To investigate the involvement of TRPV1 and associated immune responses in FECD.
- To identify key genes and pathways linking TRPV1 to FECD.
Main Methods:
- Utilized an in vitro FECD model with H₂O₂ induction.
- Analyzed gene expression microarray datasets (GSE142538, GSE112039, E-GEAD-399 & 564).
- Performed functional analyses on TRPV1-related differentially expressed genes (DEGs) and in vitro validation.
Main Results:
- TRPV1 was significantly upregulated in the in vitro FECD model.
- A negative correlation was observed between TRPV1 expression and immune cells, particularly regulatory T cells (Tregs).
- Identified four core TRPV1-related genes (MAPK14, GNB1, GNAQ, ARRB2) and implicated TRP-regulated calcium transport and inflammatory pathways.
Conclusions:
- TRPV1 and immune regulation exhibit potential crosstalk in FECD pathogenesis.
- The identified biomarkers and pathways offer a novel framework for FECD research and therapeutic development.
Abstract:
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.

