Using Zebrafish to Research Human Diseases

Zebrafish may only measure a few centimeters, but they’re invaluable for conducting basic research. Neurobiologist Stephan Neuhauss uses the unassuming animals as model organisms to investigate fundamental biological processes such as eye development as well as disorders of the eye and brain.

Zebrafish are small, sturdy and easy to keep. They are very fertile and their embryos are transparent, which makes it possible to observe how cells and organs develop. These characteristics and their genetic similarity to humans have promoted zebrafish to one of the most widely used model organisms in genetic and developmental biology research.

Stephan Neuhauss and his team at the Department of Molecular Life Sciences conduct research on zebrafish. The researchers’ focus is on the zebrafish eye and the genes that are required for the development and functioning of the animals’ visual organ. From a very early stage, zebrafish have excellent eyesight. The sensory cells in their retina work in a very similar way to those in the human eye, since these fish are also active during daylight. This makes zebrafish ideal objects of research to find out how the eyes and brain work together and to investigate the causes of eye disorders.

The researchers thus bred a line of fish in which the gene for a key transport protein in the retina was eliminated. This resulted in a visual pigment no longer sufficiently regenerating, which in turn means that the retina in these modified fish gets thinner as they age. The animals thus exhibit signs of retina degeneration as observed in humans, which can also be linked to mutations of the same gene. The scientists’ long-term goal is to find new diagnostic methods and therapeutic approaches for hereditary eye diseases.

Another key part of zebrafish research is on examining the genetic causes of epilepsy. The researchers’ attention here is focused on a protein that regulates the length and scope of neural activity in the brain by removing glutamate between nerve cells. If this protein is damaged, the neural transmitter accumulates in the synaptic gaps and the stimulation of brain networks is thrown off balance.

This kind of neural overstimulation can also be observed in lines of zebrafish in which the genetic blueprint for the relevant protein has been eliminated. Recurring spontaneous seizures or triggered by light occur in the brains of zebrafish larvae – comparable to epileptic seizures in humans. As a result, these fish behave very differently to their genetically unmodified counterparts. The researchers’ next goal is to curb this overstimulation in the brain.

In his latest project, Stephan Neuhauss plans to develop a zebrafish model to investigate malignant brain tumors in children and test new drugs for effective treatments.