- Vol. 43 No. 06
- Volume 43
- Issue 06
Investigating strains on ONH tissue key to unraveling mystery of glaucoma
Investigations of the biomechanical changes in the optic nerve head may eventually lead to improvements in therapies for patients with glaucoma.
By Lynda Charters; Reviewed by C. Ross Ethier, PhD
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.
Dr. Ethier
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.
The ONH
This structure is a major player in glaucoma, and the importance of determining why it is vulnerable to pressure, among other forces, cannot be overemphasized. Computational modeling of the ONH predicts high mechanical strains in the ONH tissues, indicating that the ONH is a weak spot in the otherwise tough corneoscleral shell, Dr. Ethier demonstrated.
Image 1. A slice through the lamina cribrosa as seen by OCT. (Image courtesy of C. Ross Ethier, PhD)
Experimentally, micro-computed tomography 3-D imaging of the ONH region of an enucleated porcine eye showed the strains that occurred when the eye was subjected to different IOP levels. For example, the anterior and posterior lamina cribrosa within the ONH undergo significant stretching and compression as IOP increases, corresponding to deformations thought to exceed safe ranges that the cells can tolerate.
Cerebrospinal fluid pressure also can affect strains in the ONH. “We know that when looking at the average or peak strains in the lamina cribrosa or in the retrolaminar neural tissue just posterior to the lamina, the strains are well outside of the safe ranges, especially in the retrolaminar neural tissue,” Dr. Ethier said.