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Hyperactive PDGFRβ signaling induces cataractogenesis via TGFβ and STAT5-IGF1
Jesse J Reardon1, Yixuan Ma2, Nathaniel S Grabinski1
1The Comprehensive Cancer Center, The Ohio State University, Columbus, OH, USA; Department of Radiation Oncology, The Ohio State University, Columbus, OH, USA.
Developmental Biology
|September 15, 2025
Summary
Platelet-derived growth factor receptor beta (PDGFRβ) activation causes cataracts by promoting lens fibrosis. This involves extracellular matrix changes mediated by TGFβ, Wnt/β-catenin, SOCS2, and STAT5-IGF1 signaling pathways.
Area of Science:
- Ophthalmology
- Cell Biology
- Molecular Biology
Background:
- Cataracts are a leading cause of reversible blindness globally.
- Lens epithelial cell proliferation and extracellular matrix overproduction contribute to cataractogenesis.
- The role of platelet-derived growth factor receptor beta (PDGFRβ) in lens fibrosis remains largely unknown.
Purpose of the Study:
- To investigate the role of hyperactivated PDGFRβ in cataract formation using a mouse model.
- To elucidate the molecular mechanisms underlying PDGFRβ-induced cataractogenesis and lens fibrosis.
Main Methods:
- Utilized a Fsp1-cre;Pdgfrb+/D849V mouse model with conditional PDGFRβ hyperactivation.
- Performed microscopic visualization, RNA sequencing, and gene set enrichment analysis on mouse lenses.
- Conducted mechanistic investigations on isolated lenses from affected and control mice.
Main Results:
- Fsp1-cre;Pdgfrb+/D849V mice developed complete lens opacification by 15 weeks.
- Histology revealed structural changes in the lens.
- RNA sequencing identified enrichment of extracellular matrix-related gene sets.
- Identified TGFβ, Wnt/β-catenin, SOCS2, and STAT5-IGF1 signaling as key mediators.
Conclusions:
- PDGFRβ promotes cataractogenesis through pro-fibrotic extracellular matrix modulation.
- TGFβ, Wnt/β-catenin, SOCS2, and STAT5-IGF1 signaling pathways are implicated in PDGFRβ-induced lens fibrosis.
- Further research is needed to explore therapeutic targeting of these pathways for cataract prevention.
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