Early neuronal changes may be biomarkers for glaucoma

San Francisco-A team of researchers may soon be able to catch glaucoma cases early by spotting nerve damage, said Andrew D. Huberman, PhD, as he provided an update on the work of the Glaucoma Research Foundation’s Catalyst for a Cure Biomarkers Initiative at the Glaucoma 360 New Horizons Forum.

“Our goal is to better monitor disease progression,” said Dr. Huberman, who is assistant professor, Department of Neurosciences, Division of Biological Sciences, Department of Ophthalmology, University of California, San Diego. “We have called this effort ‘the canary in the coal mine.’”

Traditionally, clinicians have used such techniques as eye charts and computed tomography to monitor glaucoma. These approaches, however, do not reveal much about retinal ganglion cell damage, which plays a key role in the disease, Dr. Huberman said.

“You can’t see the ganglion cells because the resolution of traditional imaging just isn’t there yet,” he said. “We need to be able to see the cells.”

If they could count the cells at different points in time, ophthalmologists could tell whether they were dying, he said.

In a mouse model of glaucoma, researchers used genetics to make ganglions glow green, allowing the scientists to observe them, Dr. Huberman said.

“We have asked this question: ‘Are there any ganglion types that are impacted first in glaucoma?’” he posed.

In answer to this question, Dr. Huberman and his team identified “off” ganglions, which fire when lights dim. In the glaucoma model in mice, these cells appear to die earlier than “on” ganglions that fire when lights brighten.

“We think this is an important discovery in our biomarker initiative,” he said.

As a next step, the team is trying to determine whether human patients with glaucoma experience a change in the way they perceive dimming lights.

At the same time, the researchers have noticed that the “off” cells place their connections within a different depth in the retina than the “on” cells. Specifically, they are located in the same layer as the microvasculature.

“We’re wondering if this is the issue,” Dr. Huberman said. “Vascular cells close to these ganglion cells may be-may be-the primary insult in glaucoma.”

As for observing the ganglions themselves, the researchers are struggling to overcome a fundamental problem.

“Unfortunately or fortunately, nature designed the ganglion cells to be clear so that light can pass to the back of the eye,” Dr. Huberman said. “So they are very difficult to image.”

His team has high hopes for the use of adaptive optics, a technique of correcting ocular aberrations, which are distortions in the light wavefront passing through the pupil. Adaptive optics can greatly enhance the resolution of an image.

“That’s where we are headed, and we definitely feel this is a goal that’s within reach,” he said.

Success in imaging the retinal ganglion cells could lead to insights into other diseases beside glaucoma, such as Alzheimer’s disease, because retinal ganglion cells are linked to the rest of the nervous system, Dr. Huberman said.

He said the Catalyst for a Cure owes its success to a multidisciplinary approach. He works closely with Jeff Goldberg, MD, PhD, professor of ophthalmology at the University of California, San Diego; Vivek Srinivasan, PhD, assistant professor of biomedical engineering at the University of California, Davis; and Alfredo Dubra, PhD, assistant professor of ophthalmology at the Medical College of Wisconsin.

“We look forward to this stuff being used in patients very soon,” he said. “We’re happy with our progress, but we’re certainly not satisfied.”