In first, scientists regenerate optic nerve

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 Patti Jacobs at: [email protected] [email protected]

Schepens Eye Research Institute is an affiliate of Harvard Medical School and the largest independent research institute in the world.

From Schepens Eye Research Institute

116 COMMENTS

  1. My son is 15 years old. He has optic nerve atrophy from a shunt malfunction at the age of 6 months. We have been told that his retina’s are normal. We would love nothing more than for him to see again. Please add us to your list. His neuro opthamologist said there is testing going on that regenerates the optic nerves. He said my son would be a candidate. Can you help him? He seems to see somethings in his peripheral vision up close and certain colors such as red with a white background. Thank you so much.

  2. i hav lost my right eye vision wen i got hurt wen i fell down in cycle and doctors said optic nerve is damaged and nothing can be done 5 yrs before but 2 yrs back i got hit by a hard ball yo my left eye and i vomitted. doctors said u hav got moth problem thats it & gav some tablets..nw am facing brain problems and absence of mind ….am nt able to analyse, understand any situations due to this ..am feeling my life is stopped and is stable ..am nt feeling happy sad nothing..wat shall i do?? plzmail me [email protected]

  3. I developed a virus and that sent my optic nerves into developing optic neuritis. My left optic nerve atrophied. This all happened Memorial Weekend 2011. It is now November 2011. I am only 38 years old, a mother of two boys, and going to school full time for Health Information Technology. My right optic nerve is swollen, but the doctor will not treat it, I have to suffer. I am afraid that I am going to be blind soon in both eyes. My right eye still has 20/20 vision, but is blurry at times. I am at my wits end right now and I have no options. If someone could help, that would be great!

    Thank you,
    Toni

  4. My child is 6months old now he had brain bleeding while he is one month old which affected his optic nerve , is there any chance to help him ?

  5. My elder brother met an accident and the optic nerve of the left eye got damaged. we got him treated everywhere there we got any hope but still not got the vision back.
    please suggest me any place in the world where we can take him for the vision. because his nerves are active a bit as he can recognize the light coming from which direction and can also see unclear words or alphabets.

  6. i am a 56y/o retired reg. nurse – i can see shapes and shadows in certain areas of my right dominant eye – my left eye is slowly developing cataract – causation factor was diabetic strangulation and glaucoma – a pressure relief valve was installed and present internal pressure is an 8 – this occured 3 yrsago and accelerated retirement under protestwith the technological need for accurate computer skills ( i dont want to accidentally injury anyone) i am welltrained for observation and recording changes in data – i think i could be of use to u in your research and i would derive immense benefit in any improvement

  7. Hello, my name is Michelle and I was doing some periodic research and saw your inquiry. My husband is blind due to his optic nerve being severed. Did you get any reply to your question about human study?

    I had emailed Dr. Chen, the author of the above study, some months back, and she told me she thinks they are about two years away from experimenting on primates, which is an FDA requirement. My husband lost his sight about 18 years ago, and at that time we were told blindness due to a severed optic nerve is permanent; they have made great strides!

  8. I’m sorry to hear about your friend. My little 13 year old brother was in a dirt bike accident and he too had swelling of the brain which caused damage to the optic nerve. He lost his sight in his right eye. I am curious to whether anyone wrote you back about humans being able to participate in this research. I would love for my little brother to see again with both of his eyes.

    Amanda

  9. Firstly i would like to say that i am pleased with this research and was interested in whether it could help me as i have suffered in a car accident 4 years ago in which i lost my accident. in my opinon i bellive that before i was opeate on i did have sight but am not 100% sure matybe it was my imagination as previously doctors have told me. The doctors that i have spoke to have given me a variety of answers some saying it has been streched some saying that it has been damaged and some saying it has been cut. i would be very interested in this optic nerve testing so if you please get back to me by contacting me on my email address or mobile number which are [email protected] and number is 07788681005
    Thankyou.

  10. I would be intersted in any optic nerve testing. I am 32 years old, brain trauma victim, blind in the right eye, partail sight loss in left eye. If anything is available, please contact me! I would appreciate any help offered!
    Thank you, David

  11. This research sounds wonderful. I have a friend who sustained injuries in a motorcycle accident about a year ago. One of his injuries resulted in swelling of the brain which caused damage to the optic nerve. As a result he lost his sight. I was wondering how someone in his situation could become qualified for participation in such research, if this is possible? I talked to him just last night and he informed me of this research and asked if I might inquire upon his behalf. If this type of participation would be possible please contact me at the above listed email address. Thank You!

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