Deciphering cellular and tissue responses in glaucoma are key to preventing and curing the disease. Some recent insights into the behavior of cells subjected to mechanical insult due to increased intraocular pressure (IOP) and changes in the stiffness of the sclera are helping to unravel the secrets of glaucoma.
One important observation is that the cells in the optic nerve head (ONH) are sensitive to mechanical changes.
“In general, cells are mechanosensitive and will, for example, migrate to a preferred substrate stiffness,” said C. Ross Ethier, PhD, the Lawrence L. Gellerstedt, Jr., Chair in Bioengineering, Georgia Research Alliance Eminent Scholar in Biomechanics and Mechanobiology, and professor of biomedical engineering, Georgia Institute of Technology/Emory University, Atlanta.
Dr. Ethier provided an example of this preferential activity. When a cell is released from the soft side of a gel, the cell migrates to the stiff side of the gel. In the opposite scenario, when the cell is released on the stiff side of the gel, the cell does not move to the soft side.
“This behavior tells you that cells have the ability to sense the mechanical properties of their substrate and respond to them,” Dr. Ethier emphasized. “We now know that substrate stiffness influences cellular growth, motility, apoptosis, and even differentiation of stem cells.”
All of these activities have shown investigators that nearly all cell types contain sophisticated machinery for sensing and responding to mechanical stimuli, he explained.
One such cellular system is the YAP-TAZ pathway, which, in addition to responding to substrate stiffness, also responds to the softness and stiffness of three-dimensional (3-D) matrices and stretching resulting from pressure, which is relevant to the ONH.