Drug ‘cocktail’ could restore vision in optic nerve injury

regenerating optic nerves cropped
Gene therapy achieved extensive optic nerve regeneration, as shown in white, but adding a potassium channel blocking drug was the step needed to restore visual function. In the future, it might be possible to skip gene therapy and inject growth factors directly. (Fengfeng Bei, PhD, Boston Children’s Hospital)

When Zhigang He, PhD, started a lab at Boston Children’s Hospital 15 years ago, he hoped to find a way to regenerate nerve fibers in people with spinal cord injury. As a proxy, he studied optic nerve injury, which causes blindness in glaucoma — a condition affecting more than four million Americans — and sometimes in head trauma.

By experimenting with different growth-promoting genes and blocking natural growth inhibitors, he was able to get optic nerve fibers, or axons, to grow to greater and greater lengths in mice. But what about vision? Could the animals see?

“The question was, is this regenerating axon functional?” says He, who is part of Boston Children’s Department of Neurology and F.M. Kirby Neurobiology Center.

Other teams, including the lab of Larry Benowitz, PhD, at Boston Children’s, have been able to achieve partial vision. But they’ve relied on genetic techniques that can only be done in a lab, and methods have involved deleting or blocking tumor suppressor genes, which encourages regeneration but could also promote cancer.

A study published today by Cell, led by He and Michela Fagiolini, PhD, demonstrates that vision can be restored using an approach that could realistically be applied in the clinic and does not interfere with tumor suppressor genes.
optomotor assay for vision testing

In optomotor tests, above, previously blind mice turned their heads to follow patterns of moving bars after given the treatment. “By making the bars thinner and thinner, we found that the animals could not only see, but they improved significantly in how well they could see,” says Fagiolini.

Getting nerves to conduct

He, Fagiolini and colleagues started with gene therapy to deliver three key growth factors (osteopontin, insulin-like growth factor 1 and ciliary neurotrophic factor. This approach got axons to regenerate and even form connections, or synapses, with their target cells in the brain. But the axons weren’t able to carry signals all the way from the eye to the brain, because they lacked myelin, an insulating sheath that helps propagate nerve signals over long distances.

“We found that the regenerated axons are not myelinated and have very poor conduction — the travel speed is not high enough to support vision,” says He. “We needed some way to overcome this issue.”

Turning to the medical literature, they learned that a potassium channel blocker, 4-aminopyridine (4-AP), helps strengthen nerve signals when myelin is absent. The drug is marketed as AMPYRA for multiple sclerosis, which also involves a loss of myelin. When they added it, the signals were able to go the distance.

L-R: Henry Lee, Fengfeng Bei, Zhigang He, Michela Fagiolini
L-R: Henry Lee, Fengfeng Bei, Zhigang He, Michela Fagiolini

A paradigm for treating glaucoma and optic nerve injury

While the study used a gene therapy virus called AAV to deliver the growth factors, He and Fagiolini are testing whether injecting a “cocktail” of growth factor proteins directly into the eye could be equally effective.

“We’re trying to better understand the mechanisms and how often the proteins would have to be injected,” says He. “The gene therapy virus we used is approved for clinical study in eye disease, but a medication would be even better.”

With regeneration kick-started, 4-AP or a similar drug could then be given systemically to maintain nerve conduction. Because 4-AP has potential side effects including seizures if given chronically, He and Fagiolini have begun testing derivatives (not yet FDA-approved) that are potentially safer for long-term use.

And they’re further testing the mice to better understand the extent of visual recovery and whether their approach might get myelin to regrow over time.

“The drugs might need to be paired with visual training to facilitate recovery,” says Fagiolini. “But now we have a paradigm to push forward.”

Fengfeng Bei, PhD, and Hing Cheong (Henry) Lee, PhD, of the F.M. Kirby Neurobiology Center at Boston Children’s, were co-first authors on the paper. The study was supported by the National Eye Institute (NIH grant EY021526), the Miriam and Sheldon G. Adelson Medical Research Foundation and the Georgetown Center for Brain Plasticity and Recovery.

He & Fagiolini Graphical abstract

  • Daphne Marks Taylor

    I have slight residual damage in my optic nerve from a cavernoma that hemorrhaged. Would this be a possible option to restore the damage in my optic nerve?

    • nansona

      Thanks for asking, Daphne. This is definitely the researchers’ goal for the future, but so far this treatment has only been attempted in animal models. Their next goal is to demonstrate that it works in people but this would likely take some years… sooner rather than later, we hope! –Nancy Fliesler, editor

      • Daphne Marks Taylor

        Thank you for your response and that’s great news! Is there a way I can be notified of progress somehow? I’d even consider being a test candidate.

      • Evandro

        Would that work for optic neuromielytis or devic syndrome?
        Thank you in advance.

  • Stefanie

    The optic nerve of my left eye got injured by a retrobulbar anaesthetic injection within refractive surgery of the eye. Visual field loss is 90%, concentric defect. Would this be a possible treatment for me someday to expand the visual field and restore vision?

    • Kuram

      I am in the same situration with the field of vision.
      I cannot drive due to this so I’m looking for a cure.
      Hope I can find a solution.

  • anita speirs

    Hi my grandson has been registered blind at the age of 1 year old. This was due to optic nerve damage on both sides after having strep b meningitis at two weeks old. please tell me this could possibly help him. thank you

    • nansona

      Thanks for writing, Anita. The researchers hope their work will lead to a treatment in the future, but so far it has only been attempted in animal
      models. Showing it works in people will likely take some years… sooner rather than later, we hope!
      Best of luck to your grandson. –Nancy Fliesler, editor

  • João Santos

    Hi! I I’m blind from glaucoma and from what I’ve “read” around the retinal ganglian cells die shortly after their axons are damaged, meaning mine are most likely dead. Doesn’t this mean that this treatment would have to be combined with stem cell therapy in order to regenerate a functioning optic nerve?

  • Dara Molloy

    Hi I have an eye disease dominant optic atrophy that effects the optic nerve would this treatment help?!

    • nansona


    • nansona

      Hi, Dara, thanks for writing. It’s hard to say yet whether this treatment would help, as it has only been attempted in animal models. The researchers hope to test it in people but it may take many years before they get there.

  • David Klein

    I too, am very interested in your research for I have optic nerve damage. In 1992, I had a small case of optic neuritis in my right eye. But the main damage came in 1995 when, (within a 48 hour period) I lost a great deal of vision in my left eye due to the optic nerve going bad. I’ve been to three neuro ophthalmologist and none of them could tell me what the exact cause is. I’ve had several brain scans and none of them showed any problems with my brain nerves. If I can help you in any way, please call or write me. david.klein@citizensbank.com
    Thanks for your work.

  • Melly

    Thank you for your work. My 14 year old son has advanced glaucoma in his right eye. And we are having continued issues and serious concerns with his eye health. It is really inhibiting his quality of life.

    We really appreciate what you are doing for others to help people have a better quality of life. We keenly watch your research developments and hope that it can be useful for our boy and for the so many others who are needing medical assistance. We hope that we can be updated of all progress. Thanks again. hugs xx

    • nansona

      Thanks, Melly. We hope this can move to the clinic! Search this site from time to time, as we will certainly report any major new developments. All the best to you and your son. Best, Nancy Fliesler (Vector editor)

  • Lisa Walton

    Our 8 yr old daughter was involved in a MVA on Dec 30, 2015, with TBI, left femer Fractured, etc..she was diagnosed with optic nerve damage in both eyes however has lost vision in her right eye, and has only central vision in her left, my husband and I are still trying to grasp all of her injuries, her spirit is warm yet she wants to see again, will your treatment be of interest to our Daughter? Thanks!

    • Melting in Phoenix

      Hi Lisa. I also lost about 98% of vision in my eye due to a MVA just two months earlier than your daughter, on 10/23. Skull fragments stretch my nerve and, as you know, those things just don’t return back to normal. I can’t see lights, even when staring directly into the sun and can basically only see the “shapes” of things (like a dark photo on a light-colored wall, or the blades going around on a ceiling fan). I can see maybe 1-2% better out of the side of my eye, and can usually distinguish “some” light…like a blinking digital clock in a dark room. Does your daughter have the same problems…albeit much worse I’m sure since both of her eyes are affected? I doubt I’ll ever be able to see clearly out of it again…or even good enough to recognize a loved one when standing right in front of me. And I mostly say that due to my 45 years of age. Your daughter is much younger so if/when a treatment is available, she’ll be put way ahead of me in line : ) I just have to remain thankful I not only lived, but only lost half of my sight, and not an arm or leg. Best wishes to your daughter. And, of course, don’t get into a vehicle with a drunk driver and always wear your seatbelt, as it’s a life-changing mistake.

    • nansona

      Yes, I think this treatment (so far only attempted in animal models) would be relevant to any kind of optic nerve damage. Hopefully the researchers will be able to show it works in people too – but this may take some years. All best to your daughter and to you. Nancy Fliesler (Vector editor)

  • Cedric Taylor

    How long can a person keep their vision with 90% of optic nerve damage?

  • Veera

    Hi one day suddenly I woke up with blurred vision in my right eye (I was blind with left eye by birth) and when went to emergency, ophthalmologist found inflammation in optic nerve and tha t caused proof of vision loss and I had only central vision and very blurred peripheral vision. It improved little bit in 2 months but not much gained in vision. After 3 months, visited one of the renowned nuero-opthalmology hospital in the world and after tests, they found nerve swelling gone but optic nerve tissues got damage and hence I still did not get vision back and seems optic nerve got shrunk. Doctors decided its typical neuritis or optic Neuropathy and there is no treatment at this moment.
    I am really looking for life saving news because I had only one eye but it got damaged now.
    Are there any treatment or medicine or food supplements to recover back from this optic nerve damage or to regenerate nerve tissues ?

    • Toni

      I have complete vision loss in my left eye as well due to optic nerve damage stemmed from optic or retinitis from a acute bout of meningitis and encephalitis in 1997.

      Have you found any possible treatment that can restore your vision?

  • Michelle

    My father had giant cell arteritis. He lost approximately 90% vision in both eyes. He is 70 y/o and in amazing health. Is there a trial he could participate in? We would try anything that would just improve vision. We are willing to travel. Thank You

  • Tom

    I have nf1 with harmatomas on the optic nerve. I had cataract surgery in my left eye. I had an ocular occlusion of the eye 6 yrs ago. Recently went to the eye doctor and was told in the front of the eye its perfect and I should have 20/20 vision. Its the back of the eye where the nerve is palour in colour. And the surrounding arteries or Vessels are narrowing. This probably would not cure the tumor suppression issues with the 17 chromosome. My question is can it bring back the centeral vision? Btw i do have perfial vision in the same eye with no central vision. Kindly advise

    • Tom

      I have a follow up question .. but some history back in 1986 I suffered radial and ulnar nerve damage due to open reduction of a multi break of the left humerus. The doctors tried electronic stimulating the nerves to make them work and regenerate. Took almost 3 years to heal both the bone and nerve… at first the electronic stimulation was painful until they were able to dial back the charge and allow healing of nerve and regain function of the arm. So my question is why can’t the same principle be applied to the optic nerves

  • Bertha DellaSala

    HI, i lost my left eye vision due to a meningioma that had grown out of control and part of it lodged on my left optic nerve. 80% of the tumor was removed and this made the eye have full blindness. I know that this is just now being tested in animal, but hoping that this new treatment with little side effects and stem cell combined can bring a cure. This has limited me in so many ways, but no matter what i keep going and don’t give up. Thanks for your work.

  • Shelton Minor

    Such powerful stories and testimonials from some incredible people who just want answers. I wish there was a way we could form our own support group. I am a professional photographer who onced photographed 3 of our Presidents at the same time. I am one of the few in the world to do this and now I see this blessing fading away like the rest of my career.

  • Pradeep Shah

    My little 3 year old grand nephew had his Optical Nerve damaged as a reult very blurry vision if at all and also has problem in walking and swallowing as Doctors have messed him up from Day 1 How do we cure him?

  • Kelly Nemecek

    This is interesting. My left eye became blind in 2004 from bacterial meningitis. I am 50 now, it seems improbable it can ever be fixed in my lifetime.

  • Vanessa Henry

    My daughter lost her site due to a brain cancer. The doctors say her optic nerve is now white instead of yellow/orange. Is this something eventually that would work for her? Her optic nerve was not severed at all just died basically because of the brain pressure.

  • Taryn Caldwell

    My girlfriend was shot on her left side of her head like right behind her eye so it damaged her eye socket and came out the right side of her head behind her eye .. Her right eye was taken out and her left eye finally closed due to the swelling going down. They said she only had 3 out of 6 nerves in the right eye so they needed to remove it. I just want to know are there anything ideas to improve her left eye so she’ll be able to see ?

  • Matthew Thorne

    Hi, I have a optical glioma which means that I have damage to my optic nerve although, I do have light perception in the left eye and reduced vision in the right. Would it be possible to remove the tumor and then regenerate the optic nerve so that I get full vision? If this is not possible currently, how long do you think it might potentially be until this is achievable?

  • Ardeshir Viccaji

    I have a brave friend in Pakistan who has been blind for several years due initially to retinitis pigmentosa ( not sure of spelling) and on inquiry find that optical nerve damage also exists. I see very little progress on re generation in the last 4 years , mainly restricted to tests on mice. Please HELP/ ADVISE. This guy is really plucky ( and even gives tuitions ) but there are limits to HOPE.

  • Linda Chapa Hearrell

    Hi where are you guys with this research? My son is 16 and was born with a cataract in his left eye. I am hoping with today’s technology something can be done to help correct hus vision. Please email me lhearrell@gmail.com my phone is 832-766-7410. Thank you.

  • Dana

    Is there any update on this research for 2017? Has it progressed into anything that might work in anything other than lab mice?
    I have a friend that has Optic Neuritis due to a Brain Radiation and MS.( not sure what caused the damage) both eyes are affected, one is worse than the other.

  • Cathy Newman

    I have a 6 month old daughter born with Septo-Optic dysplasia and Optic Nerve Hypoplasia, underdeveloped optic nerves, she is totally blind in the right eye and can see some light and shade in the left. Is this something that could help her in the future ?

  • Naush Malik







  • Lori

    My husband Tim has lost 50%vision in one eye and 35%in the other due to optic neuropathy two and a half years ago and had to quit his job after 30years and go on disability. We too are looking for something to help get his vision restored. I have contacted a doctor in Florida that was doing a clinical trial, but he was not ready yet. Now, after not being able to hunt, he has decided he wants to try something. I have called the NEI, but have gotten no response. Wondering if there is another avenue to try or how to get ahold of the right people to see what might be available to help him. Thanks, Lori

    • Kimberly Orr

      Son electrocuted with 12,470 volts to forehead in October 2016. Has complete loss of vision (optical nerve damage) in left. Blurred vision in right. Any updates on this? We live in Michigan. Willing to travel anywhere for answers. He is 22 and wants to get back to work as a lineman.

  • Benjamin Blue

    I suffered an injury 7 years ago, I was kidnapped and assaulted. My skull was crushed and optic nerve destroyed. I’ve had complete vision loss in that eye since day one.

    It’s surprising how little research I’ve done all these years – almost none. I’ve finally started, and am trying to learn as much as I can about my injury. I’m not sure where to start!

    One assumption I’ve made is mine is quite rare – I’ve yet to meet anyone with this. Also, I haven’t looked. It seems that I have the end result most in common with glaucoma patients.

    I appreciate this article and suppose it could shine a little bit of hope, although I proceed with extreme caution. Any ideas, links, resources, you can share with me, for learning about my injury, community, etc, would be greatly appreciated.

    Be well,

  • Kim Papp Monihen

    I have been researching any type of treatment that would help my friend that had a hip replacement that went terribly wrong and ended up with extremely high levels of cobalt (the highest they have seen). She is actually lucky to be alive, however it damaged her optic nerves and she is now blind, and has also had some hearing loss. The blindness is what is the most debilitating
    for her. Would this type of treatment work for her if it would be available in the near future? I do know she would be willing to be a test subject…she is willing to do anything with the possibility to be able to see again.