Extracellular Matrix Stiffness Modulates Myopia Scleral Remodeling Through Integrin/F-Actin/YAP Axis

Area of Science:

• Ophthalmology
• Cell Biology
• Biomechanics

Background:

• Scleral extracellular matrix (ECM) remodeling and reduced stiffness are hallmarks of myopia.
• Understanding the mechanisms of scleral remodeling is crucial for myopia research.

Purpose of the Study:

• To investigate the mechanisms of scleral remodeling regulated by mechanical signals from the ECM.
• To elucidate the role of YES-associated protein (YAP) in myopia pathogenesis.

Main Methods:

• Western blot (WB) and ELISA to confirm YAP expression in human and guinea pig myopia models.
• In vitro experiments using stiff (50 kPa) and soft (8 kPa) substrates to mimic myopia biomechanics.
• Quantitative real-time RT-PCR, WB, and fluorescence staining to investigate molecular mechanisms.
• In vivo studies with YAP activator/inhibitor and F-actin facilitator to assess therapeutic potential.

Main Results:

• YAP expression is reduced in the sclera of myopic individuals and guinea pigs.
• YAP acts as a mechanotransducer, modulating collagen expression under mechanical stimuli.
• Integrin α1β1 regulates YAP via F-actin cytoskeleton modification, influencing YAP nuclear translocation.
• This pathway leads to the suppression of COL1A1 expression.

Conclusions:

• The integrin α1β1-F-actin-YAP-COL1A1 axis is a critical regulatory mechanism in myopia pathogenesis.
• Targeting this pathway may offer novel therapeutic strategies for myopia.