Piezo1 Activation by Shear Stress Induces Corneal Epithelial Homeostasis Disruption

Area of Science:

• Ophthalmology
• Cell Biology
• Biophysics

Background:

• Abnormal blinking induces shear stress, disrupting tear film stability and corneal health.
• The role of mechanosensors, like Piezo1, in ocular surface homeostasis under shear stress is not fully understood.

Purpose of the Study:

• To investigate the impact of shear stress on corneal epithelial cells.
• To elucidate the role of the mechanosensor Piezo1 in mediating these shear stress-induced effects.

Main Methods:

• In vivo mouse models and in vitro human corneal epithelial cell cultures were used to simulate shear stress.
• Piezo1 activity was modulated using pharmacological agents and genetic knockdown.
• Cellular responses including proliferation, migration, barrier function, and pyroptosis were assessed.

Main Results:

• Shear stress activated Piezo1, influencing cell proliferation and migration.
• Low shear stress promoted tight junction formation, while high shear stress compromised barrier function and induced pyroptosis.
• Piezo1 knockdown reversed the detrimental effects of shear stress on corneal epithelial cells.

Conclusions:

• Piezo1 acts as a critical mechanosensor mediating intensity-dependent responses to ocular shear stress.
• High-intensity shear stress via Piezo1 activation leads to corneal barrier dysfunction and pyroptosis.
• Targeting Piezo1 presents a potential therapeutic strategy for shear stress-related ocular surface diseases.