While transplants involving organs such as the heart and lungs have been conducted successfully for years now, those involving sensory organs like the eyeballs are yet to become a reality because scientists have not figured out how to reconnect them to the brain. However, a new study, in which blind tadpoles were able to use transplanted eyes on their tails to see, suggests there might be another way to restore sight in human beings.
One of the major challenges in regenerative medicine involves figuring out how to promote innervation, or the supply of nerves, to a body part. Of interest is whether there is another way to integrate a sensory organ into the nervous system without connecting all the neurons.
Building on previous work in which they showed that transplanted eyes located outside the head were able to register limited sensitivity to light, scientists at Tufts University wanted to find out if the results could be improved and if there was another way to stimulate nerve growth, specifically by using zolmitriptan, a migraine treatment drug that influences serotonin levels and neural development.
To do so, they took the eyes from embryonic tadpoles, transplanted just one into the tails of blind tadpoles at the same stage of development, and dosed some with zolmitriptan. Experiments were then conducted to test their ability to distinguish different colors, specifically, red and blue.
Using a box with a series of chambers into which they could swim, the researchers trained the tadpoles to associate red with a mild electric shock so they'd swim into one with a blue space, the idea here being that only those that could see would be able to pass the test. What they found was that of the batch that had been dosed with the drug, 29 percent were able to differentiate between the colors, while only 11 percent of untreated tadpoles with eye grafts succeeded. In contrast, 76 percent of normal tadpoles were able to pass the test.
The tadpoles were also tested for true image-forming vision, that is, the ability to follow patterns. This was done by placing them in a Petri dish that was sitting on top of a monitor screen with rotating triangular clusters. Again, the blind tadpoles with untreated eye grafts fell behind the others. Only 38 percent of them were able to follow the patterns, compared to 57 percent of those that had been treated with zolmitriptan. In contrast, 80 percent of tadpoles with normal vision were successful.
What do these results mean? For a start, they show that the eye transplants were able to deliver sensory information even though they were not connected to the brain.
"The fact that the grafted eyes in our model system could transmit visual information, even when direct connections to the brain were absent, suggests the central nervous system contains a remarkable ability to adapt to changes both in function and connectivity," says co-author Douglas Blackiston, a post-doctoral associate at Tufts University.
During the study, the researchers also found that the treated specimens grew new nerves that provided the central nervous system with sensory input without making changes to the tadpoles' original nervous system. The fact that zolmitriptan could stimulate the growth of neural connections in these animals suggests drugs used to treat neurological and psychiatric diseases could potentially be repurposed for use in regenerative procedures involving organ transplants.
"For regenerative medicine to move forward and enable the repair of damaged tissues and organ systems, we need to understand how to promote innervation and integration of transplanted organs," says study author Michael Levin, a regenerative and developmental biologist. "This research helps illuminate one way to promote innervation and establish neural connections between a host central nervous system and an implant, using a human-approved small molecule drug."
While it's still too early to apply these findings to human beings, what this new study confirms is the brain's plasticity and its ability to adapt to extreme changes in the body, in this case, eyes that were connected to the spinal cord instead of the brain.
While scientists have not figured out how to connect sensory organs to the brain yet, what these findings suggest is that there might not be any need to do so. As the authors note, the brain is not only plastic enough to make use of visual data no matter where in the body it originates, but can also do it when the data is communicated to the spinal cord. This suggests that biomedical implants might not require brain surgery to connect them to the nervous system, but could instead provide sensory data from other parts of the body that carry lower surgery risk.
The study was published in npj Regenerative Medicine and Levin talks about the findings in the video below.
Source: Tufts University