A school of small fish

Examining regeneration through a fish’s eye

When someone’s optic nerve is damaged – by glaucoma or inflammation of the nerve, for example – their eyesight goes with it. The nerve can’t be healed, and vision loss can’t be restored.

That’s not the case for fish, which can regenerate their optic nerve in as little as 12 days and regain their eyesight 80 days after an injury.

Ava Udvadia, an associate professor of biological sciences in the College of Letters & Science, wondered why. So she took a novel approach to studying the genetic mechanisms fish use in healing optic nerve damage.

“In the past, people looked at regeneration as a single event,” Udvadia says. “Our approach looked at it as actually being a series of events.”

Ava Udvadia
Ava Udvadia

She and her team looked at key points in the fish’s regeneration timeline. They included the point where the neuron grew past its initial injury; when the regenerated axon grew past the junction with the other optic nerve; and when the axon connected to the correct part of the fish’s brain.

More than 7,000 genes were involved in the regeneration process. The researchers categorized which genes’ expressions peaked during the early, middle and later portions of the process, so they could identify what mechanisms regulated those particular genes.

They discovered sequences within a fish’s genetic information that could tell the cell which genes to turn on and off for regeneration, and when to do it. They also learned about changes in “transcription factors” – chemicals that bind to the DNA and control the genes for regeneration.

With the fish’s regeneration-associated gene programming identified and its regulatory sequences uncovered, Udvadia now faces a new task.

“If we can identify from among these transcription factors which ones are different in the response in mammals and fish, now we’re at a place to define what we need to tweak in mammals to get them to switch this program on,” Udvadia said.

She hopes her research will open avenues for treating eye injuries in humans and other mammals.