It is also known that zebrafish possess
the ability to induce self-repair of their damaged retinas with restoration of
vision in a few weeks.
‘Discovery of retinal repair mechanism in zebrafish opens up new treatment possibility for retinal degeneration in humans.’
Interestingly, the structure of the
retinas of fish and mammals are quite similar. The retina is very thin - less
than 0.5 millimeters thick, but it contains three layers of nerve cells or
photoreceptors that detect the light, horizontal cells that process the signals
from the photoreceptors and ganglion cells that receive the visual information
and transmit it to the brain.
This prompted the research team to
determine the mechanism that led to self-repair of damaged retinas in zebrafish
and its potential application in human retinal degeneration.
Role
of Muller Glia in Retinal Repair in Fish
The retina consists of a
special type of adult stem cell, the Müller
glia, that span all the three layers providing mechanical strength as well
as electrical insulation. They have been found to also play a key role in
repair of retinal cells. When
regeneration
is stimulated, the Muller
glia dedifferentiate (regress from a specialized state to a
simpler state), and start to divide, and then differentiate into replacements
for the different types of damaged nerve cells. Muller glia are
also found in human retinas, but have not been shown to regenerate.
What
Induces Muller Glia To Differentiate
Earlier studies have found
GABA, an inhibitory neurotransmitter to
influence stem cell activity in mouse hippocampus. The study authors were
inspired by the results to determine whether a similar mechanism might operate
in the zebrafish retina inducing the Muller glia to differentiate.
Methods
and Findings of the Study
The team tried out their hypothesis in
two ways:
- They blinded zebrafish and then injected them with drugs that
caused increased GABA release and
- They injected normal
zebrafish with an enzyme that lowers the GABA levels in their eyes.
"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 Muller 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."
Zebrafish can be easily blinded. If they
remain in total darkness for several days and then exposed to very bright
light, it results in the destruction of all the photoreceptors in their eyes.
However, because of their robust regenerative capacity, vision is restored in
just 28 days.
- When the biologists injected drugs that increased GABA levels in the blinded fish, they found that it suppressed the reparative process.
- When they injected an enzyme that reduces GABA concentrations in the eyes of normal fish, the Muller
glia began dedifferentiating and dividing, marking the first step in 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 James Patton, Stevenson Professor of Biological Sciences at Vanderbilt, who
directed the study. "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."
Newfound
Role for Inhibitory Neurotransmitter GABA
The authors are excited by the results of
their study since another recently published study has shown that GABA
concentrations influence regeneration of pancreas cells too.
"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."
Future
Research Plans
Following the results of their current
study, the team plan to determine in both zebrafish and mice whether
- GABA could cause differentiation that leads to the formation of
new photoreceptors and other specialized nerve cells in the retina.
Reference
- Fish eyes may hold key to regenerating human
retinas - (https://news.vanderbilt.edu/2017/03/09/fish-eyes-may-hold-key-to-regenerating-human-retinas)
Source: Medindia
