The trabecular meshwork (TM) responsible for IOP homeostasis in the eye could sense the IOP fluctuations dynamically and adapt to the mechanical changes appropriately. Cationic mechanosensitive channels (CMCs) have been reported with critical roles in mediating the TM responding to many mechanical forces. However, the mechanism of how CMCs influence the TM cellular function in aqueous humor drainage and against mechanical damage is still elusive. Gene ontology enrichment analysis demonstrated that prohibition of CMCs significantly influenced the mechanical changes in the TM, such as store-operated calcium channel activity, microtubule cytoskeleton polarity, toll-like receptor signaling pathway, and neuron cell fate specification. Our results indicated that they might be the critical downstream signals of CMCs adapting to mechanical forces and mediating AH outflow.