Optogenetic Stimulation for Axonal Regeneration

Richard Lee, MD, PhD Bascom Palmer Eye Institute


Glaucoma is an eye disease that is associated with damage to retinal ganglion cells (RGCs) and the connections of these cells to the brain that allow for vision. Using a method to specifically stimulate damaged RGCs, Dr. Lee’s team has forced these cells to regrow new connections toward the brain after damage. The goal of the team is to use this new method of stimulation to prevent RGCs from losing these brain connections by allowing them to maintain these brain connections and, therefore, preserve vision.

Project Details

Nerve cells that die in the eye due to glaucoma normally do not regrow, resulting in irreversible blindness. This research project uses new molecular genetic approaches to force dying nerve cells to grow new nerve connections.

Glaucoma is associated with the permanent loss of nerve cells in the eye which allow for vision. One of the first signs of glaucoma is the loss of the connections from eye nerve cells to the areas of the brain responsible for vision. This project identifies the time course and pattern of nerve connection loss and uses a novel method to force regrowth of new nerve connections that could lead to recovery of vision.

Using newly developed, cutting edge technologies, Dr. Lee’s team was able to image the nerve connections in the eyes of animals with acute injury to the nerve cells in the retina. This imaging technique is a modified version of the optical coherence tomography (OCT) technology that is currently being used on the human eye for clinical quantification of nerve tissue in the clinic. In addition, the team genetically engineered animal nerve cells that can be directly imaged in the live animal and followed over the time in a manner that is not possible in the human eye, but which provides important information to correlate nerve cell loss with nerve connection (axon) loss.

Dr. Lee’s team is using a newly developed genetic stimulation model to force the growth of nerve connections from injured nerve cells in the live animal model. By understanding the natural time course of vision loss in this acute nerve injury model of glaucoma, the team could follow treatment interventions in the same animal over time in a manner not possible in the past. This combination of genetic and technological innovation has not been used in the past and forms a powerful new platform through which Dr. Lee’s team will identify and test multiple types of treatments to protect nerves and nerve connections from degenerating due to glaucoma.