In a groundbreaking experiment involving 3-day-old tadpoles, researchers at Tufts University in Medford, Massachusetts, found an innovative way to speed up the innervation process of transplanted organs.
To test their theory, the scientists chose to conduct their investigation on frogs because their molecular structure resembles that of humans.
The team successfully restored vision in blinded tadpoles by perfecting a technique that allowed the grafted eyes — transplanted on the animals's tails rather than on their heads — to quickly grow nerves and reintegrate in the nervous system by connecting directly to the spinal cord.
The study, published March 30 in npj Regenerative Medicine, offers conclusive proof that eyes — and, in all probability, other sensory organs as well — can function in optimum conditions without necessarily being attached to the brain.
In view of the highly promising results, researchers believe their findings could one day be applied to transplant patients receiving bioengineered tissues, organs or even limbs.
"If a human had an eye implanted on their back connected to their spinal cord, would the human be able to see out of that eye? My guess is probably yes," says Michael Levin, study author and biologist at the university's Allen Discovery Center.
Eyeing The Tail
The ingenious experimentation owes its success to a pharmaceutical compound which the team previously found out could remarkably expedite neural development in amphibians.
The drug, called Zolmitriptan, is generally used in the treatment of migraines and proved to be extremely efficient in supporting the innervation of transplanted organs.
Levin's team began by grafting eyes on 38 blind African clawed frog tadpoles, with each recipient having a single eye implanted on its tail. The donor eyes were harvested from other tadpoles which had the same age as the transplant "patients."
The compound's nerve regenerative power was confirmed when Levin applied the drug to some of the newly grafted eyes right after transplant and later compared the results with the control group.
Researchers discovered that, eight days after surgery, 40 percent of tadpoles who were administered the drug developed fresh neurons which safely connected to the central nervous system. By comparison, only 5 percent of tadpoles that didn't receive Zolmitriptan reached the same outcome.
Color and visual acuity tests revealed the drug led to full vision recovery in the treated tadpoles, which outperformed the ones that didn't get the compound, and were able to distinguish between differently colored areas and avoid colored triangles moving on a screen beneath them.
From Tail-Eyes To Neck-Ears: What The Future May Hold
The active ingredients in Zolmitriptan work by stimulating particular serotonin receptors, which in turn trigger electrical impulses at a cellular level. This allows grafted tissue to form new neural connections that tune in to the nervous system by directly embedding in the spinal cord.
This explains why Levin's team chose the tadpoles's tails as a transplantation site, as opposed to the head: their procedure aimed to produce visual sensory restoration while bypassing the brain.
"We have no idea how we would connect a retina to the brain, and if you wanted to replace an ear, you would have to cut out a big piece of the skull," states Bernd Fritzsch, from the University of Iowa.
The new study eliminates the need for such concerns, opening up new horizons in the transplant of both harvested and bioengineered organs — from bladders, hearts, and tracheas through to eyes, ears and sensitive skin — which scientists could implant anywhere on the body, "on the neck, for example, and connect it to the spinal cord."
"It might look funny, but it could still work," says Fritzsch, who points out further studies are needed to analyze if the drug retains its regenerative effects when used on human nerves as well.
