Published online 8 September 2008 | Nature | doi:10.1038/news.2008.1088

News

Retinal transplants see fleeting success

But efficacy and practicality of the procedure are called into question.

eyeRetina transplants could potentially save the sight of millions.Corbis

It was six months after her operation that Elisabeth Bryant first started to see the effects, quite literally. Clinically blind, Bryant began to make out the swinging pendulum of her grandfather clock from across the room. Since then her vision improved to the point that she could read large print editions of Reader's Digest, send emails and continue with past activities like sewing and knitting.

Bryant is one of ten patients to have received a retinal transplant as part of a phase II trial to replace diseased photoreceptors in conditions such as retinitis pigmentosa (RP) and age-related macular degeneration (AMD). Before the transplant she could see nothing but shadows. But within a year her vision had improved from 20/800 to 20/160, a remarkable recovery.

Each of the patients in the trial received a small 4 millimetre square of retinal tissue, complete with retinal progenitor cells and the retinal pigment epithelium that nourishes them. The tissues were placed in the sub-retinal space beneath the fovea, the area of the retina responsible for sharp central vision.

Seven of the subjects experienced an improvement in their visual acuity, says Norman Radtke, the ophthalmologist who carried out the surgery at the Retina Vitreous Resource Center in Louisville, Kentucky. The results are reported in the August issue of the American Journal of Ophthalmology1.

Faint hope

The results may appear to improve the chances of restoring vision in sufferers of RP and AMD — the most common causes of blindness in developed countries, affecting millions of people. But it is far from clear just how much hope this research really offers.

"I think this approach will never work as a standard clinical therapy," says Marco Zarbin director of the Institute of Ophthalmology and Visual Sciences at New Jersey Medical School, in Newark. One reason is the fact that the transplanted tissue is obtained from aborted fetuses, he says. "Even if it proves to work wonderfully, the number of patients that would need to be treated worldwide or even in the United States alone would be in the millions." There simply wouldn't be enough donors available, and the logistics of getting the ethical approval to use them would act as a major barrier to treatment.

Another concern is the efficacy of the procedure. Despite 20 years of research on animals by co-authors Robert Aramant at research firm Ocular Transplantation, also in Louisville, and Magdalene Seiler at the University of California, Irvine, there is still no clear evidence that the improved vision in humans is directly due to the transplanted photoreceptor cells replacing the function of host cells within the retina.

The transplanted grafts are made up of the entire thickness of the donor retina, says Robert MacLaren, a vitreoretinal surgeon at Moorfields Eye Hospital, in London. This means that for synaptic connections to form between the donor photoreceptors with the host retina, they would have to grow through several layers of donor cells. And despite rigorous post-operative testing, there is no evidence of this, he says, nor of any blood vessels growing to keep the graft alive.

"An alternative explanation is that the graft is releasing growth factors that are aiding the recovery of dying host photoreceptors," says MacLaren. If true, it may be simpler to introduce these growth factors instead.

Fleeting vision

In animals, there is evidence for synaptic connections forming, says Aramant, but this is difficult to establish in humans. "For now, nobody can say to what extent we have a rescue effect in humans," he says.

And there is another major issue. The improved visual acuity seems to only last for a couple of years. Six years on after her transplant, Bryant's visual acuity has now dropped down to 20/320. "There may be a time limit on how effective this might be," says Radtke. "That is a legitimate concern."

The real value of this trial is the demonstration that cells can be placed in the sub-retinal space without any adverse reaction, says Zarbin. This holds promise for other possible forms of cell-based treatment currently being explored, such as introducing stem cells into the retina and getting them to differentiate into new photoreceptors. 

  • References

    1. Radtke, N. D. et al. Am. J. Ophthalmology 146, 172-182 (2008). | Article |
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