Transcriptome Changes Driving Multiple Regulatory Pathways Involved in TGF-β-Induced Anterior Subcapsular Cataract

Area of Science:

• Ophthalmology
• Molecular Biology
• Genetics

Background:

• Transforming Growth Factor-beta (TGF-β) is implicated in lens epithelial-mesenchymal transition (EMT) and fibrosis, key processes in anterior subcapsular cataract (ASC) formation.
• The specific impact of active TGF-β1 overexpression on the lens epithelial transcriptome has remained largely undefined.

Purpose of the Study:

• To comprehensively characterize the lens epithelial transcriptome in response to TGF-β1 overexpression.
• To identify novel downstream genes and pathways involved in TGF-β1-induced cataractogenesis.

Main Methods:

• High-throughput RNA-sequencing was performed on isolated lens epithelia from two independent TGF-β1-overexpression transgenic mouse lines (OVE853, OVE918) and wild-type controls.
• Differential gene expression analysis identified commonly altered genes between transgenic lines.
• Comparative transcriptomic analyses were conducted with existing lens datasets and pathway/gene ontology tools.

Main Results:

• 384 differentially expressed genes (DEGs) were commonly identified in both TGF-β1 transgenic lines compared to wild-type.
• Elevated DEGs were associated with EMT, inflammation, extracellular matrix organization, and mechano-sensation.
• Reduced DEGs were linked to lipid metabolism, Wnt-suppression, and Bmp-/Notch-activation.
• Overlapping pathological pathways were found with a mouse cataract surgery model, and endoplasmic reticulum stress genes were consistent with human ASC data.

Conclusions:

• This study provides the first comprehensive transcriptomic analysis of two independent TGF-β1 transgenic ASC models.
• Identified DEGs and pathways offer novel insights into the molecular mechanisms of TGF-β1-driven cataract formation.
• The data is accessible via iSyTE for further research.