Piezo2 mechanically regulate scleral fibroblast differentiation by activating relA/RhoA pathway

Area of Science:

• Ophthalmology
• Cell Biology
• Biophysics

Background:

• Myopia involves scleral remodeling driven by biomechanical changes and fibroblast differentiation.
• Understanding the molecular mechanisms of scleral remodeling is key to myopia research.

Purpose of the Study:

• Investigate the role of Piezo2 in form-deprivation myopia (FDM).
• Elucidate Piezo2's mechanism in regulating alpha-smooth muscle actin (α-SMA) expression.

Main Methods:

• Established a guinea pig FDM model.
• Analyzed Piezo2 expression via qRT-PCR and Western blotting.
• Utilized cyclic stretch on scleral fibroblasts, assessing RhoA, relA, Calpain, and α-SMA levels after siRNA knockdown.

Main Results:

• Increased Piezo2 expression observed in myopia sclera and stretch-stimulated fibroblasts.
• Cyclic stretch upregulated RhoA, relA, and α-SMA, alongside increased Ca2+ influx and calpain activity.
• Inhibition of Piezo2 or Ca2+ influx abolished stretch-induced upregulation; SiRelA reduced RhoA expression.

Conclusions:

• Piezo2 functions as a mechanotransduction ion channel in myopia.
• Modulates the Ca2+-dependent relA/RhoA pathway, essential for fibroblast to myofibroblast differentiation.
• This pathway is critical for myopia scleral remodeling.