ZEBRA FISH: A PROMINENT ANIMAL MODEL IN CLINICAL RESEARCH

 

ZEBRA FISH: A PROMINENT ANIMAL MODEL IN CLINICAL RESEARCH

INTRODUCTION

An animal model is a non-human species that can reproduce aspects of a disease found in humans/attributes of human diseases used in medical research. These animals models are used because they will provide information regarding the development, progression of a disease and how a medical intervention will perform in human clinical trials before they are given to humans; also to provide a sound basis for making determinations about reasonable safety and efficacy of an investigational drug product in the clinical trials, especially preclinical studies which heavily rely upon animal models of human disease.  Researchers may perform experiments that would be impractical or ethically forbidden in humans by using animals. The use of animal models in science has contributed to the advancement of understanding and the successful treatment of the symptoms and cures of diseases.

A wide range of animal models have been used over the last century, such as mice, rats, rabbits, dogs, cats, non-human primates, and other animals, but the costs of research are high, particularly with mammals. Therefore, a new model for animal experiments, including invertebrates and species of fish, has recently become essential. Thus, as a result of searching for potential new experimental models, the zebrafish was discovered in order to minimize costs and save time. As a result, in recent years, the use of zebrafish (Danio rerio) has increased its popularity as an experimental animal model in the field of biomedical research. The xenograft models are animals with transplanted human cancers or other tissues. 

WHY DO ZEBRAFISH MAKE SUCH GOOD ANIMAL MODELS?

Zebrafish are being used more extensively in research due to its various useful properties:

Ø  Benefits of Zebra Fish:

o   The zebrafish is small, robust, and significantly less expensive with low maintenance costs. Their ideal conditions can easily be simulated since they are naturally found in ponds.

o   Zebrafish produces hundreds of offspring with an adequate supply of embryos to study at weekly intervals.

o   The Zebra fish's embryo grows quicker than the human embryo in a month's span.

o   Zebrafish embryos are almost translucent, allowing the development of internal structures to be easily studied, and only with a low-power microscope any blood vessel in a the zebrafish embryo is easily seen.

o   It is an excellent model organism for researching early development since zebrafish eggs are fertilized and grown outside the mother's body.

o   Zebrafish have a similar genetic structure sharing 70% of genes with humans and it is also considered to have 84% of genes linked with human disease.

o   Since zebrafish are vertebrates, they have the same organs, tissues and share many characteristics with human systems such as  muscle, blood, kidneys and eyes.

o   The Zebra fish has an in-built capacity to repair its own heart muscles when damaged. If part of their heart is removed, they will develop it back within a matter of weeks. The specific factors involved in this process will help us to develop ways of repairing the heart in humans with heart failure.

o   The Zebra fish has a high-quality genomic sequence. This has facilitated scientists to create mutations to research their role in more than 14,000 genes. The genetic engineering of these enables them to express a spectrum of human and/or disease-relevant genes in zebrafish larvae. You can make zebrafish glow in various colours in the dark by genetic modification.

LIMITATIONS

o   Heterogenic respiratory and reproductive system. Thus, it is difficult to use zebrafish as a model for respiration or reproduction in humans; several mammalian organs are not present including breast tissue, lungs, prostate and skin lacks certain cellular components present in humans.

o   Since zebrafish live in aquatic habitats, the screening of water-soluble drugs is another downside.

o   Physiology is not identical to humans as it is poikilothermic (cold-blooded) and developing embryos lack a placenta, this means that some drugs may be metabolized in a different manner.

o   They are greatly influenced by several environmental factors such as temperature, lighting, population density, water quality and nutrition. In order to interpret the data accurately these variables must be tightly controlled.

o   They are evolutionarily distant from humans and many genes are present as two copies, creating extra work to determine functional roles.

WHY ARE ZEBRAFISH A CRITICAL RESEARCH MODEL AND HOW DO THEY IMPACT DRUG DISCOVERY AND DEVELOPMENT?

Zebrafish is a game-changer for drug research and development that advises optimal disease care. For example, a human tumor specimen may be implanted in Zebrafish, and information on drug tolerance and metastases will be available within five days to help guide medication selection before or immediately after treatment begins. Healthcare expenditure is out of sight. Zebrafish provides a low-cost, high-volume way to assess which drugs currently being tested are worth taking to the next phase of development. Sufficient funding for Zebrafish research will increase the speed at which we learn about new therapeutic agents and the pace at which these drugs reach the development phase and, eventually, the patients who need them. 

APPLICATIONS OF ZEBRAFISH IN VARIOUS DISEASE MODELS

Researchers have found several things about the development of organs from zebrafish. New genes that cause human diseases have been discovered, as well as new drugs that can be used to treat patients. Achievements obtained by comparing human and zebrafish genomes include the identification of many previously unknown genes implicated in rare types of muscular dystrophy, genetic mechanisms involved in human embryo growth and cardiac physiology, and medications that are currently being investigated as potential therapies for skin cancer.

Zebrafish is the ideal model to study various ailments. Diseases currently being studied through Zebrafish research include Cancer, Diabetes, Hematopoiesis, Gastrointestinal Diseases, Epilepsy, Autism, Cardiac Diseases like myocardial infarction, lipid-related diseases including atherosclerosis, obesity, diabetes and hepatic steatosis, Central nervous system disorders in humans include Parkinson's disease, schizophrenia, Alzheimer's disease, and depression, Kidney disorders like polycystic kidney disease, muscular disorders and also leukemia.

Additionally, Regeneration Studies that provides the information regarding complex tissue regeneration process following any injuries, Immuno and Inflammatory responses, Wound Healing, Angiogenesis and vasculature, Cell survival and apoptosis. Zebrafish are being tested for rare genetic disorders such as Prader-Willi Syndrome, as well as for the impact of environmental toxins on human neurological development. They are also used in toxicological studies, aquaculture and also as a supplement to other model organisms (phenotyping in mice).

CONCLUSION

It can be concluded that zebrafish is a successful and versatile animal and are an important biomedical model in every aspect of biology. The usefulness of zebrafish is because of its low cost and easy maintenance, transparent embryo, easy manipulation, high reproductive rate, and rapid embryonic development. Extensive research on zebrafish has proved its supremacy as a model for human diseases over other conventional models, but still, they stand on an underdeveloped platform with uncovered potentials as there is still much to discover about this species. Therefore, it is necessary to put more efforts so that the available new information can flow to the understanding of biomedical research combined with the use of zebrafish. The present focus should mainly be on establishing zebrafish as an alternative preclinical drug discovery model.

--By

Bhargavi Neela (Pharm.D)

Student at Clinosol Research Pvt. LTD