Gene therapy has markedly improved vision in both eyes in three women who were born virtually blind. The patients can now avoid obstacles even in dim light, read large print and recognize people's faces. The operation, researchers predict, should work even better in children and adolescents blinded by the same condition.

The advance, reported in the February 8 issue of Science Translational Medicine, extends earlier work by the same group. Between 2008 and 2011, Jean Bennett of the University of Pennsylvania's Mahoney Institute of Neurological Sciences and her colleagues used gene therapy to treat blindness in 12 adults and children with Leber's congenital amaurosis (LCA), a rare inherited eye disease that destroys vision by killing photoreceptors—light-sensitive cells in the retina at the back of the eye. Typically, afflicted children start life with poor vision, which worsens as more and more photoreceptors die.

The treatment grew out of the understanding that people with the disorder become blind because of genetic mutations in retinal cells. One mutated gene that causes the disorder is named RPE65. An enzyme encoded by RPE65 helps break down a derivative of vitamin A called retinol into a substance that photoreceptors need to detect light and send signals to the brain. Mutant forms of RPE65 prevent the production of this enzyme in a "nursery" layer of cells called the retinal pigment epithelium, which is attached to the retina and nourishes photoreceptors by breaking down retinol, among other cellular services.

In the initial study, retina specialist and Bennett's co-author Albert Maguire of Penn Medicine injected a harmless virus carrying normal copies of RPE65 into an area of the retinal pigment epithelium, which subsequently began producing the enzyme. In each of the 12 patients, Maguire treated one eye—the one with worse vision. Six patients improved so much they no longer met the criteria for legal blindness.

In the new study, Maguire injected the functional genes into the previously untreated eye in three of the women from the first group. Bennett followed the patients for six months after their surgeries. The women's vision in their previously untreated eye improved as soon as two weeks after the operation: They could navigate an obstacle course, even in dim light, avoiding objects that had tripped them up before, as well as recognize people's faces and read large signs. Bennett showed that not only were the women's eyes much more sensitive to light, their brains were much more responsive to optical input as well. Functional magnetic imaging showed regions of their visual cortices that had remained offline before gene therapy began to light up.

Surprisingly, Bennett reports, the second round of gene therapy further strengthened the brain's response to the initially treated eye as well as the newly treated one. "That wasn't something we had been expecting, but it makes sense because the two eyes act in concert, and some aspects of vision rely on binocularity." In the new paper, the authors suggest that neuroplasticity plays a role: It is possible that regions of the visual cortex responding to the newly flowing channel of information from the second eye bolster activity in areas of the visual cortex responding to the initially treated eye.

An institutional review board required that Bennett work with adults in the follow-up study, but she thinks the therapy will work even better in younger patients who have not lost as many photoreceptors. She says the results "really bode well" for restoring meaningful vision to people with LCA and other forms of inherited blindness.

8 Comments

1. 1. DennyGH 07:15 PM 2/8/12

   This is a very interesting area of research. I'm wondering if work like this is being done for people afflicted with macular degeneration?

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2. 2. alan6302 in reply to DennyGH 10:15 PM 2/8/12

   I think there are vitamins for that

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3. 3. imvrf 12:09 AM 2/9/12

   I am curious whether this has any application for those with retinopathy of prematurity.

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4. 4. TigerWild 08:10 AM 2/9/12

   I am curious if there is a vision or thought adjustment in persons who have what would be condisdered normal vision. For the sake of pure science, they should extend the trials into persons NOT afflicted with the mutated RPE65 and report the results. It would be truly awesome to find another method that enhances vision past laser enhancement. Maybe it could correct color blindness, etc!

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5. 5. santaidm 09:20 AM 2/9/12

   My own sister is afflicted by the cone and rod disease which is similar to LCA. That too can be fixed using gene therapy. The problem lies with identifying the exact gene that causes the problem. In her case Dr Robert Koenekoop has narrowed down the gene location to a very small area and he believes he will identify the gene in a matter of a few weeks/months.
   
   Once this is done the rest of the procedure is well established and working well, so there is hope.
   
   I certainly do not want to induce false hopes but I think that macular degeration is also being looked at as well as a number of other diseases.
   
   And Vitamin A, Lutein and Omega 3 are also appropriate to prevent further damage while awaiting treatment. I am not a health professional and my post is only intended to inform others that there are possibilities.

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6. 6. gmperkins 04:14 PM 2/9/12

   @DennyGH There is and is an article in a past SciAm on that topic. If memory serves, a virus was altered and then injected into muscle tissue. The virus would invade muscle cells and start producing a protein that basically says 'grow more muscle'.
   
   @TigerWild The retina is like the film, to improve eyesight we'd need a better lens, lens manipulation or our eye would need to be able to better reshape itself. Laser surgery modifies the cornea in ways that bend light to better fit ones eye shape. Perhaps denser retina cells would provide more detail but that would go well beyond gene therapy. Same goes for, say, a larger & more flexible lens combined with bigger eyes.

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7. 7. Nonstickron 12:12 PM 3/6/12

   My 9 year old daughter has Optic Nerve Hypoplasia. This sounds a lot more promising and realistic than the magic stem cell injections the chinese wanted to sell us. I hope they move toward researching that aspect of blindness with this method.

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8. 8. Hopefultom 09:37 AM 3/9/12

   How is it possible to " restore " vision to someone who never had it in the first place ?

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