Neurons fight back early in brain disease

David Calkins, PhD, vice chair and director of Research at the Vanderbilt Eye Institute, said it was previously believed that, as retinal activity is lost, the connection between the retina and the brain should be gone.

But the opposite is true.

"The dogma has been that, once started, neurodegenerative disease is a one-way path," said Calkins, Denis O'Day Professor of Ophthalmology and Visual Sciences and director of the Vanderbilt Vision Research Center. "What we have demonstrated is that the brain fights back. We found that individual neurons fight back to maintain signaling between brain regions, thereby slowing progression. It's a balance between disease and adaptation."

"And we found that the mechanism that causes this response actually preserves vision for a brief period of time, despite the onslaught of stress in glaucoma. We think we can develop new therapies based on this mechanism to keep the optic nerve signaling, which will maintain vision even as a disease progresses."

The team used a model of glaucoma, the leading cause of irreversible blindness in the world, to record and compare how the loss of synapses relates to the diminishment of signals to the axon.

Calkins' team found that the axon signals did not diminish, rather the signaling to the brain increased, meaning that neurons were fighting back against the loss of excitatory activity.

"With this information, we hope to bootstrap this natural adaptive mechanism and prolong signaling between brain regions and prevent subsequent degeneration," he said. "As long as signaling is maintained, progression slows and vision is maintained.

"Now that we have identified the mechanism that causes adaptation, we can exploit it through new drugs or even gene therapy."