Cationic Mechanosensitive Channels Mediate Trabecular Meshwork Responses to Cyclic Mechanical Stretch.

Area of Science:

• Ocular Physiology
• Cell Biology
• Biochemistry

Background:

• The trabecular meshwork (TM) maintains intraocular pressure (IOP) homeostasis by regulating aqueous humor (AH) outflow.
• Cationic mechanosensitive channels (CMCs) are implicated in the TM's response to mechanical forces, but their downstream effects remain unclear.

Purpose of the Study:

• To investigate the role of CMCs in human TM (HTM) cells under mechanical stress.
• To identify proteomic changes and signaling pathways affected by CMC inhibition in response to mechanical stretch.

Main Methods:

• Human TM cells were subjected to cyclic equiaxial stretching.
• GsMTx4, a CMC inhibitor, was used to analyze proteomic alterations.
• Gene ontology and heatmap analyses were performed on differentially expressed proteins (DEPs).

Main Results:

• CMC inhibition significantly impacted pathways including calcium channel activity, cytoskeleton polarity, and cell fate.
• 148 DEPs were identified, clustered into 21 groups.
• Key downstream signals related to calcium homeostasis, autophagy, cell cycle, and cell fate were highlighted.

Conclusions:

• CMCs are crucial for HTM cell adaptation to mechanical forces.
• Downstream signaling pathways regulated by CMCs are critical for mediating AH outflow and maintaining IOP.