Fibrotic remodelling in pterygium: Multi-omics insights and statin-mediated modulation
Aadhithiya T.Gr.,, Mathan Lohanathan, Vishnu Teja Gonugunta, Tejaswi Prasad, Ankita Kumari, Vikram Subramanian, O.G. Ramprasad, Venkatesh Prajna, Kuppamuthu Dharmalingam, Daipayan BanerjeeBackground and objectives
Pterygium is a highly prevalent conjunctival surface disorder, particularly common among outdoor workers in equatorial regions. Surgical excision remains the only current treatment option, underscoring the critical need for non-surgical pharmacological strategies. Comparative transcriptomic and proteomic studies investigating molecular alterations in pterygium pathogenesis remain limited. We conducted this study to identify key dysregulated molecular factors in pterygium and evaluate pharmacological modulation of fibrotic responses.
Methods
A multi-omics approach was employed using next-generation RNA sequencing (pterygium/control: 8/5) and shotgun mass spectrometry–based proteomics (pterygium/control: 4/4) on pterygium tissues obtained during excision surgery. Key findings were validated by quantitative PCR and Western blotting. Transforming Growth Factor Beta 1 (TGFβ1)–induced human conjunctival fibroblast and primary pterygium fibroblast culture models were used to assess the effects of statins on myofibroblast activation, cell proliferation, and migration.
Results
Functional enrichment analysis of 1,342 differentially expressed genes and 152 differentially expressed proteins revealed enrichment of pathways related to oxidative stress response, cellular oxidant detoxification, angiogenesis, complement activation, extracellular matrix organisation, cytoskeletal reorganisation, inflammation, and proteolysis. Twenty-three factors were concordantly dysregulated at both transcriptomic and proteomic levels, highlighting a core set of molecules associated with TGFβ–mediated extracellular matrix remodelling and myofibroblast activation. Pharmacological treatment with statins,–lipid-lowering drugs with pleiotropic anti-fibrotic properties–attenuated TGFβ1–induced α-smooth muscle actin expression in conjunctival fibroblasts and reduced proliferation and migration of pterygium fibroblasts in vitro .
Interpretation and conclusions
This comparative multi-omic and pharmacological analysis provides mechanistic insight into fibrotic remodelling in pterygium and suggests that statins may modulate fibroblast activation pathways relevant to disease progression.