Shear Stress as a Driver of Retinal Müller Glia Survival and Fibrotic Reprogramming

) for 24 h. Müller glia survival, morphology, and extracellular matrix (ECM) remodelling were evaluated. Expression of the mechanosensitive ion channel TRPV4, phosphorylated focal adhesion kinase (pFAK), and the pro-fibrotic cytokine TGF-β1 was analysed. TRPV4 and TGF-β1 were pharmacologically inhibited to assess their functional roles. The results showed that shear stress enhanced Müller glia survival and reduced cell area. TRPV4 expression increased under flow, and its inhibition decreased survival and reversed morphological changes. Shear stress also elevated pFAK levels in a TRPV4-dependent manner. Similarly, TGF-β1 expression increased with flow, and its inhibition decreased survival and altered cell morphology under both static and flow conditions. ECM remodelling involved increased intracellular collagen I and IV levels and enhanced fibronectin deposition, both regulated by TGF-β1. In conclusion, shear stress induces Müller glia survival, cytoskeletal remodelling, and selective ECM regulation via TRPV4 and TGF-β1. TRPV4 acts upstream through pFAK signalling, while TGF-β1 controls ECM remodelling. Together, these pathways initiate early remodelling and contraction, potentially driving retinal fibrosis post-injury. Targeting TRPV4 and TGF-β1 may offer therapeutic strategies to limit glial scarring and preserve retinal structure.