Network toxicology, transcriptomics, and cytotoxic validation reveal TDCPP-induced pterygium mechanisms

Area of Science:

• Environmental Health
• Toxicology
• Ophthalmology

Background:

• Pterygium is an ocular surface disorder linked to environmental factors like UV exposure.
• Tris(1,3-dichloro-2-propyl) phosphate (TDCPP), an organophosphate flame retardant, is found in environmental and biological samples.
• The role of TDCPP in pterygium pathogenesis is not well understood.

Purpose of the Study:

• To investigate the molecular mechanisms linking TDCPP exposure to pterygium development.
• To identify potential therapeutic targets for TDCPP-associated ocular surface disorders.

Main Methods:

• Integrative approach: network toxicology, transcriptome sequencing, in vitro cytotoxicity assays.
• Bioinformatics analysis to identify TDCPP targets and pterygium-associated genes.
• Weighted gene co-expression network analysis (WGCNA) and molecular docking simulations.
• In vitro experiments using human conjunctival fibroblasts.

Main Results:

• Identified 43 overlapping genes between TDCPP targets and pterygium genes.
• Highlighted MMP3 as a central regulator in pterygium pathogenesis.
• Confirmed stable interactions between TDCPP and MMP3 via molecular simulations.
• Low-dose TDCPP upregulated MMP3, enhancing fibroblast proliferation; high-dose induced cytotoxicity.

Conclusions:

• TDCPP promotes pterygium pathogenesis through MMP3-mediated extracellular matrix remodeling and fibroblast proliferation.
• MMP3 is identified as a potential therapeutic target for TDCPP-related ocular surface disorders.
• This study offers insights into the environmental etiology of pterygium.