Discovering neural repair genes for glaucoma

Glaucoma is one of the leading causes of blindness for individuals over the age of 60. It occurs when the optic nerve, which connects the eye to the brain, is damaged from high eye pressure—a process called neurodegeneration.

The symptoms of glaucoma can start slowly, for example affecting patients’ peripheral vision first, causing the disease to often go unnoticed. While there is no current cure to reverse the damage of glaucoma, methods like lowering eye pressure are used to slow or prevent the progression of total vision loss. 

“While lowering intraocular pressure is the standard treatment for glaucoma, there are no therapies that directly treat the optic nerve neurodegeneration and loss of vision,” said Yang Hu, MD, PhD, associate professor of ophthalmology. “Repair genes that lead to neuroprotection and even regeneration are desperately needed.”

In the early part of the COVID-19 pandemic, Hu and his collaborators finally experienced a breakthrough in their findings. These collaborators included multiple members from Hu’s lab in the Mary M. and Sash A. Spencer Center for Vision Research at the Byers Eye Institute at Stanford: Liang Li, PhD, Fang Fang, MD, PhD, Xue Feng, PhD, Haoliang Huang, MSc, Liang Liu, Pingting Liu, PhD, Adam Z. Xu, and Pei Zhuang, PhD. 

They also collaborated with Stanley Qi, PhD, associate professor of bioengineering, and Le Cong, PhD, assistant professor of pathology and genetics.

The group knew that when the gene Pten is deleted in retinal ganglion cells (RGCs), this promotes optic nerve regeneration. However, only a small percentage of cells have the potential to regenerate. The team's initial breakthrough came when Fang discovered a surgical technique that allowed them to identify those few regenerating RGCs. The group’s findings were recently

 published in the high-impact journal Neuron.

In parallel experiments, the team has uncovered gene therapies and even small molecule drug therapies that stand to protect against degeneration further. “Another group of findings led us to discover that interfering with retinal neurons’ stress response blocks these cells from dying,” Hu said. His team is now exploring how to best formulate and even combine therapies to initiate a translational research program that can move into human testing.

“We are thrilled by these findings because they show great potential that we are on the brink of creating a promising neuroprotection therapy for glaucoma patients,” Hu said.

Their long-term goal is to move these research findings into clinical trials, and until then, they will continue to study cell development.

By KATHRYN SILL

Kathryn Sill is the former web and communications specialist for the Byers Eye Institute in the Department of Ophthalmology, at Stanford University School of Medicine.