Scientists Regenerate Optic Nerve for the First Time
BOSTON, Mar. 7 -- For the first time, scientists have regenerated a damaged optic nerve -- the nerve that connects the eye to the brain.
This achievement, which occurred in laboratory mice and is described in the March 1, 2005 issue
of the Journal of Cell Science, holds great promise for victims of diseases
that destroy the optic nerve and
for sufferers of central nervous system injuries. "For us, this is a dream
becoming reality," says Dr. Dong Feng Chen, lead author of the study,
assistant scientist at Schepens Eye Research Institute and an assistant
professor
of ophthalmology at Harvard Medical School. "This is the closest science has
come to regenerating so many nerve fibers over a long distance to reach
their
targets and to repair a nerve previously considered irreparably damaged."
This research, supported in part by grants from the National Institutes of
Health, the Department of Defense and the Massachusetts Lions Club, has
always
been a priority of the institute, but recently the urgency around it has
increased, according to Dr. Michael Gilmore, director of research at
Schepens
Eye Research Institute and professor of ophthalmology at Harvard Medical
School. In addition to the thousands of Americans blinded by glaucoma and
injuries
that destroy the optic nerve, "We were hearing stories of soldiers in the
Middle East whose lives were saved by body armor, but who were returning
with
severe damage to limbs and eyes," he says. "At the same time, we learned of
the untimely death of Christopher Reeve. It was, therefore, a priority for
us to redouble our efforts to find ways to restore damaged nerves."
Many tissues in the body continually renew themselves if injured. However,
this is not true for nerve cells or their fibers (axons) in the Central
Nervous
System (CNS). The optic nerve, which is part of the CNS, loses this ability
shortly before birth. So for those afflicted by
glaucoma,
which destroys the optic nerve through excessive internal pressure, or those
with injuries that sever the optic nerve after birth, destruction can be
permanent
and blinding.
Chen and her research team dedicated themselves to learning the reasons why
CNS tissue stops regenerating and to finding ways to reverse that process,
using
the optic nerve as their research model. The optic nerve consists of
millions of nerve cells which transmit visual information from the retina to
the brain
for interpretation. In earlier research, Chen's team discovered several
processes that they believed "locked up" the optic nerve's ability to
regenerate.
The first lock, they found, was the turning off of a specific gene - BCL-2 -
which, when turned on, activates growth and regeneration. The second lock,
they theorized, was a scar on the brain created shortly after birth by
"glial" cells. (Glial cells have many functions in the brain, one of which
is to
create this kind of scar tissue). The researchers believed that the scar
puts up a physical as well as molecular barrier to regeneration. Athough
there
may be other "locks" to the regeneration door, Chen and her colleagues
believed these two were the most important. In the current research, Dr.
Kin-Sang
Cho, research associate in Chen's laboratory and the first author of the
paper, tested two keys to unlock regeneration. The first key involved the
development
of a mouse model in which the BCL-2 gene is always turned on (or is
overexpressing). The second key was the use of a mouse line carrying
mutations of "glial
specific genes" that lead to the reduced "glial scar" formation. By
unlocking the regeneration with the first key, they observed robust optic
nerve regeneration
in postnatal mice, whose nerves grew rapidly and reached from the eye to the
brain in four days. But the regeneration happens only in the younger mice
whose brains had not yet formed a "glial scar." In the mice that were
slightly older and had developed the "glial scar," regeneration failed
again. Dr.
Cho then added the second key by combining BCL-2 overexpresser with the
"glial gene" mutation to prevent the development of the "glial scar" in the
older
transgenic mice. He found that the combination of the turned-on BCL-2 and
the mutation of "glial specific genes" caused the optic nerves to return to
an
embryonic state and stimulated rapid, robust regeneration of the optic nerve
within only a few days.
"We could see that at least 40 percent of the optic nerve had been
restored," says Chen. "But we believe that an even higher percentage
actually regenerated."
The next step for Chen and her colleagues is to determine if the regenerated
optic nerves were functional. In other words, did they cause the mice to see
again?
To obtain a copy of the study, "Reestablishing the Regenerative Potential of
the Central Nervous System Axons in Postnatal Mice," e-mail Patti Jacobs at:
pjacobs12@comcast.net.
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