Scientists have unlocked a key cellular mechanism that allows fish to restore their vision which may someday lead to human treatments to spur self-repair.
A new study in Stem Cell Reports shows that researchers from Vanderbilt University discovered a unique part of the retinal regeneration process in zebrafish, which can repair lost vision in a matter of weeks.
The new research found that fluctuating levels of a neurotransmitter called GABA had a direct impact on the ability of the zebrafish to regenerate eye cells because GABA appears to either suppress or bolster — depending on how much is present — the presence of certain adult stem cells that are linked to the repair process.
The study overturns previous scientific understanding of the regeneration process. “The prevailing belief has been that the regeneration process in fish retinas is triggered by secreted growth factors, but our results indicate that the neurotransmitter GABA might initiate the process instead,” said lead author James Patton, a professor of Biological Sciences at Vanderbilt.
“All the regeneration models assume that a retina must be seriously damaged before regeneration takes place, but our studies indicate that GABA can induce this process even in undamaged retinas,” added Patton.
Basically, the researchers found that high levels of GABA in the retina result in lower concentrations of adult stem cells known as Müller glia. When GABA levels decrease, the Müller glia stem cells proliferate and turn into replacement parts for the damaged eye cells.
The research opens the door to potential treatments based on intentionally suppressing GABA levels. “This work opens new ideas for therapies for blinding diseases and has implications for the broader field of regenerative medicine,” said Tom Greenwell with the National Eye Institute, which funded the study.
Building a Case for GABA
The neurotransmitter GABA, which scientists know for its ability to limit nervous activity by suppressing nerve transmission in the brain, has recently been at the center of important stem cell research. This focus inspired the Vanderbilt University team to explore how it may be involved in retinal regeneration.
“Last month a paper was published in the journal Cell that reports GABA levels play a central role in the regeneration of pancreas cells,” said Patton. “We now have three instances where GABA is involved in regeneration – the hippocampus, the pancreas and the retina – so this could be an important, previously unknown role for the neurotransmitter.”
The burgeoning body of research, while in its relative infancy, may hold vast implications for future treatment methods.
In the current study, the researchers found that intentionally maintaining high levels of GABA in the eyes of recently blinded zebrafish limited the regeneration process. But when they lowered GABA levels, the regeneration process began without interruption.
“Our theory is that a drop in GABA concentration is the trigger for regeneration. It initiates a cascade of events that includes the activation of the Müller glia and the production of various growth factors that stimulate cell growth and proliferation,” said Patton. “If we are correct, then it might be possible to stimulate human retinas to repair themselves by treating them with a GABA inhibitor.”