The Pathological Contribution of Cell Adhesion Disruption in RGC Death

Project Summary

The goal of this research is to determine if loss of cell-to-cell, and/or cell-to-surface, contacts by RGCs stimulates the biological pathway leading to their death after damage to the optic nerve.

Cells living in a complex tissue are most healthy when they make and retain contacts with other cells, and to the extracellular environment. We know that tissue culture cells begin to die when we break those contacts. We also know that an early response of RGCs to optic nerve damage, such as you would experience in glaucoma, is to retract their appendages and shrink. A major response of cells to this process is to activate a critical death protein called BAX. We have made technological advances to be able to watch BAX become activated in living RGCs. We found an important feature of this process was their ability to reverse the BAX activation process. The only other time this is known to happen is when cells that have lost their contacts with the outside world manage to reach out and re-establish them again. Our study is focused on determining if the process of BAX activation in RGCs follows the same principles, particularly if specialized signaling pathways associated with cell-cell contact play an important role.

This work will help us understand better how optic nerve damage leads to ganglion cell death. Importantly, the evidence that the process may be reversible provides a possible way to develop a therapy that will rescue damaged cells in patients with glaucoma.