[accessibleimage] Schepens scientists regenerate optic nerve

Subject: Schepens scientists regenerate optic nerve for the first timeNew
hope for sufferers of glaucoma and spinal cord injuries


>> Public release date: 23-Feb-2005
>>
>> Contact: Patti Jacobs
>> pjacobs12@xxxxxxxxxxx
>> 617-872-0364
>> Schepens Eye Research Institute
>>
>> Schepens scientists regenerate optic nerve for the first time
>> New hope for sufferers of glaucoma and spinal cord injuries
>> Boston, Mass. - For the first time, scientists have regenerated a
>> damaged optic nerve -- from 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, which has been
>> 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 in recent times, 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, and hundreds of thousands disabled by spinal cord injuries, "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 Reeves. It was, therefore, a priority
>> for us to redouble our efforts to find ways to restore damaged
>> nerves."
>>
>> According to Senator John Kerry, who supported funding of this
>> important work, "Schepens is doing cutting-edge research that can
>> make
>> a real difference for a new generation of troops returning home with
>> nerve damage. We need to support our troops in actions, not just
>> words, and I am glad that we have been able to get funding for this
>> important work." Adds Congressman Lynch, "Last month, I visited the
>> Walter Reed Army Medical Center in Washington and met with dozens
>> of
>> service men and women who could benefit directly from the good work
>> of
>> the people at Schepens. Their vital research will not only enhance the
>> lives of our soldiers but also gives hope to every American who
>> suffers from diseases of the central nervous system."
>>
>> 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 CNS consists of the brain (of
>> which the eye and optic nerve are part) and the spinal cord. For all
>> mammals, including human beings, CNS nerves lose their ability to
>> regenerate after injury at the point in their development when they
>> are fully formed. For example, the optic nerve loses this ability
>> shortly before birth. So for those afflicted by glaucoma, which
>> destroys the optic nerve through excessive internal pressure, or with
>> injuries that sever the optic nerve after that developmental
>> milestone, destruction can be permanent and blinding.
>>
>> Chen and her research team have 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, which connects the eye to the brain, consists of
>> millions of nerve cells, which, when uninjured, 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. Although 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, for the first time,
>> they observed robust optic nerve regeneration in postnatal mice, which
>> 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--again, as
>> with the younger mice - 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?
>>
>> Chen also believes that this combination BCL-2 and scar prevention
>> technique could work to regenerate other Central Nervous System
>> tissue, increasing the possibility that spinal cord patients could
>> walk or move again.
>>
>> This work has important implications. "The possibility of restoring
>> sight following optic nerve injuries is tremendous. Fifteen percent of
>> all wartime injuries include the eye and those with optic nerve trauma
>> are the most grave. Today's medicine has little effective treatment to
>> offer and blindness is often the end result," says Retired Lieutenant
>> Colonel Robert C. Read of the Clinical Applications Division at the
>> Department of Defense's Telemedicine and Advanced Technology
>> Research
>> Center.
>>
>> "This outstanding breakthrough by Schepens scientists offers new
>> hope
>> to those who suffer from blinding diseases and injuries, including our
>> returning soldiers. The potential application of this discovery to
>> treatments for other central nervous system injuries is yet another
>> reason why I have been proud to support the Department of Defense's
>> funding of the Center for Excellence in Military Low Vision Research,"
>> stated Congressman Mike Capuano.
>>
>> Adds Congressman Stephen F. Lynch, "This extraordinary
>> breakthrough
>> demonstrates what we can achieve when we support public and private
>> partnerships between the Defense Department and the best
>> researchers
>> and scientists in the field. Because of the decades of work and
>> progress by Dr. Gilmore and Dr. Chen and the entire team at the
>> Schepens Eye Research Institute, the search for a way to repair nerve
>> damage in the human body has taken a giant leap forward."
>>
>> "I'm so pleased with the work going on at Schepens," Rep. Jim
>> McGovern
>> says. "They are on the frontiers of research that will dramatically
>> improve people's lives. And the Federal Government must continue to
>> be
>> a partner in this vital effort."
>>
>> ###
>> To obtain a copy of the study, "Reestablishing the Regenerative
>> Potential of the Central Nervous System Axons in Postnatal Mice,"
>> email
>> pjacobs12@xxxxxxxxxxxx
>>
>> Schepens Eye Research Institute is an affiliate of Harvard Medical
>> School and the largest independent eye research institute in the
>> world.
>

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