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On/Off Switches Part Two

Posted by Ilena Di Toro | Posted on December 23, 2020

In On/Off Switches Part One I wrote about research done at the Oklahoma Medical Research Foundation (OMRF) that discovered a compound that controls the growth of blood vessels. This can be utilized for conditions ranging from diabetic retinopathy to cancer. They aren’t the only ones doing this type of research. Scientists at Johns Hopkins have found that the ability for some types of animals to regrow neurons aren’t missing, as previously thought, rather it is inactivated in mammals. Conversely many fish and other cold-blooded animals have this ability.

In fact, research states that the potential for regeneration is available in mammals. “In fact, regeneration seems to be the default status,” says Seth Blackshaw, Ph.D., professor of neuroscience at the Johns Hopkins University School of Medicine. “The loss of that ability happened at multiple points on the evolutionary tree.”

To find out where in the cellular pathway regeneration stops for mammals, researchers in Blackshaw’s lab created retinal injuries in zebrafish, chickens and mice. Next they used high-powered microscopes and a gene mapping tool to see how certain retina cells, known as the Muller glia cells, respond to the injury.

Blackshaw’s team was surprised to learn that after the injury, the cells of each species entered an active state whereby specific genes were activated to contain the injury and send signals to the immune system cells to fight the invaders. Beyond that step, response for each species were different.

The Muller glia cells in zebrafish went back to a more primitive state, which allowed them to develop into other cells types, such as the ones lost to the injury. The chicken retinas activated some of the gene control switches. That means that chickens have less ability to create new Muller glia cells in the eye after an injury. As for the injury response in mice, the Muller glia cells remained in the active state for several days. In contrast, the Muller glia cells in zebrafish are active for only eight to twelve hours. Despite all this activity, mice don’t have the ability to make new neurons.

Researchers also found that the same genes that allowed the zebrafish to regenerate were ready to go in the mouse eye but that the “on” transcription factor was never activated. In fact, the nuclear factor I (NFI) blocked the cells regeneration potential.

If regeneration is such a good thing, why don’t mammals have this ability? Blackshaw suspects that animals with a higher potential to develop disease in neurological tissue may have lost this ability as a way to protect brain cells. After all, if infected brain cells were allowed to grow, they would spread the infection throughout the nervous system.

These two research projects show that sometimes there is no need to create something new. They demonstrate that looking into the cellular and genetic building blocks can one day lead to treatments that can improve outcomes for many diseases.


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