Zebrafish (Danio rerio) may seem like an unsuspecting contribution to any tropical freshwater aquarium, but this fish belonging to the minnow family (Cyprinidae) has the potential to be a lifesaver to humans due to its one extraordinary attribute – its ability to rapidly heal itself and regenerate body parts.

What Are Zebrafish?

Zebrafish are tropical freshwater fish that naturally occur in the rivers and ponds of India, Pakistan and the Himalayan region. However, they are popular pets and globally available in pet shops. The name “zebrafish” is due to the horizontal dark blue stripes on each side of their bodies, mimicking that of our land-dwelling equine friends, the zebra.

Investigating (Lack Of) Scars In Zebrafish

A wound heals when white blood cells are rapidly recruited to a wound site after tissue damage. This prevents microorganisms, like bacteria, from entering the wound, and helps coordinate wound closure. These white blood cells also clear cell and tissue debris during the repair process.

A new study was initiated in November 2020, led by researchers from the University of Bristol, that investigated the genetics of scarring and how it can be prevented. The project is worth an estimated $2 million and is funded by The Scar Free Foundation. This study is the first of its kind anywhere in the world. It aims to analyze population health data to determine the cause of scarring, while also using the rapid-healing abilities of the zebrafish as a study organism to determine the genetic components involved in healing scars. Humans and zebrafish share many genes, and the human connective tissue growth factor (CTGF) protein is nearly 90% similar in its amino acids to the CTGF protein in zebrafish.

Why Investigate Scars?

Although most scars are only minor inconveniences to most people, around 20 million people in the United Kingdom are believed to have a scar, and for some of these people their scars pose a major problem. This new study looks at those afflicted with vaccination scarring, children who have had cleft lip surgery, women with Caesarean section scars and patients with internal lung scarring. These types of scars cause physical deformities, as well as pain, itching and restricted movement, not to mention the long-lasting mental health impacts and psychological damage. This study, along with the Scar Free Foundation, therefore aims to “achieve scar-free healing within a generation and to improve the lives of those affected by scarring”.

Fishy Business

In order to look at the genetics of scarring, researchers at the University of Bristol have turned to fish genetics to search for answers. Zebrafish are rapid healers that are able to regrow and repair damaged tissues, without leaving any scars or evidence that they were injured. Zebrafish are also great research subjects, as their translucent skin (apart from their zebra stripes) allows researchers to see right inside their bodies, and witness how genes affect their behavior. This will allow the researchers to directly see which genes are activated during healing and scar formation, and also provide insight into when and where potential treatments can assist. It will show how genes can influence wound repair and also the severity of subsequent scarring.

Potential Outcomes

This study will only conclude sometime during 2025, and it hopes to identify the genetic causes of scarring. If the study is a success, the implications will be a major breakthrough. It will assist people throughout the world, and also offer a more accessible and less expensive solution to scarring (as opposed to plastic surgery). Although it is unlikely that any gene therapies that arise from the study will forever prevent scarring in humans, it can still improve the lives of millions of people.

Zebrafish May Cure Blindness, Heal Hearts And Repair Spinal Cords

Not only may zebrafish hold the genetic key to prevent scarring in the future, they have long been used in scientific and medical research to attempt to cure several ailments in humans.

Zebrafish are able to regrow the retinas in their eyes – and damage to the retina is a common cause of blindness in humans. Zebrafish are able to repair the retina and optic nerve within a week, by reducing a chemical in the fish’s brain, which triggers the healing action. Unlike other wounds on human bodies, we are not able to regenerate cells of the retina, and if it is damaged, the cells in the retina form scar tissue, which leads to blindness. In zebrafish, a group of enzymes (known as matrix metalloproteinases) work together to help the retina reconnect with the brain after optic nerve damage.

Zebrafish may also be able to assist with damages to human hearts, as these fish can repair damage to their own hearts. Researchers from the University of Oxford isolated a gene that assists Mexican tera fish with heart regeneration. When this gene was switched off in zebrafish during the same study, the fish were unable to repair their hearts without scarring, indicating the importance of this gene, which is also found in humans.

Zebrafish may also help repair human spinal cord injuries. A study published in Science by researchers from Duke University reported that zebrafish were able to completely heal their spines, even after it was severed, because of a protein that assists in rebuilding damaged spinal nerves. The study’s senior investigator, Kenneth Poss, called it “one of nature’s most remarkable feats of regeneration”. When the spinal cord of a zebrafish is severed, dozens of genes are activated, and within days, new molecules and proteins are produced to bridge the gap between the severed spine. Within 8 weeks, new nerve tissue had completely filled the gap, and the zebrafish had fully reversed its paralysis.

It will still be many years before the research done on zebrafish can be adapted for use in human healing, but the early results remain very promising. This study and the potential outcomes once again proves the value of our marine environment, and why we should do everything in our power to conserve it.