A little over 100 years ago, scientist were studying fruit flies to learn more about genetics. Since they were easy to capture and breed, scientists were able to study multiple generations in a short period of time. The information that they found lead to the mapping of regions that correspond to the fly’s physical traits.
Over time mammals, such as mice and rats, have been used in biomedical research, since they are anatomically and genetically similar to humans. When it comes to vision research, scientist have gone beyond mice and rats to utilize newts and zebrafish.
While newts are reptiles, they can regenerate body parts, including eye tissue and the nerve connections from the eye to the brain. Researchers in the lab of Katia Del Rio-Tsonis, PhD at Miami University in Oxford, Ohio are looking into how the newt can regrow its eye lens after an injury.
Unlike mice or fruit fly, newts have only been recently used in biomedical research. That means there isn’t an existing stock of animals to employ. So instead of using many newts to study the regeneration process, Del Rio-Tsonis uses optical coherence tomography (OCT) to watch the regeneration of a newt’s eye in 3D. The great thing about using OCT is that it can scan and expose parts of the eye, such as the iris, lens and retina, at high resolution, non-invasively and in real time. Also, it allows researchers to get images of the intact lens, remove it and then follow the regeneration process in the same animal.
Seeing the regeneration process of a lens in real time gives research a chance to see cells and tissues reorganizing themselves to rebuild a damaged eye. In addition, it helps to answer questions about the role the newt’s immune system and blood vessel have in the regeneration. The study of the newt’s ability to regenerate an eye lens will yield insights that can one day lead to treatments for humans.
What about zebrafish? They aren’t mammals, yet they are used in vision research, as well. In fact, scientists at the National Eye Institute (NEI) developed a zebrafish model of NEDBEH, which is a rare genetic disorder that can cause coloboma. This is a developmental defect where parts of the eye are missing. This model will help with the understanding of the eye’s embryonic development.
Uveal coloboma is when the middle layer of eye tissue, consisting of the iris, the ciliary body and the choroid, is missing. At the lower portion of the eye, there is a slit that closes during normal embryonic development. If it doesn’t close, the coloboma develops and its effect on vision ranges from slight blurriness to blindness. The cause of coloboma is not clear and part of the reason why is due to the collection of genes that must be turned on and off at critical moments in a normal eye’s development.
Researchers studied eye development in zebrafish with a mutation in the gene rerea, which is the equivalent of the human RERE gene. Compared with normal zebrafish, those with the rerea gene had enlarged optic stalks, eye tissue in the brain and coloboma. The rerea mutation changed the expression of important developmental genes. It interfered with the signaling of the shh protein. This protein directs the development of the optic stalk and retina. By inhibiting the shh pathway at a different point, researchers were able to rescue the coloboma. This led to the closure of the optic fissure.
What’s great about this model is that it helps to make clear the role the RERE gene plays in eye development. These kinds of models lead to a greater understanding of the coloboma, its mechanisms and finding the targets to reverse the defects.
Both research projects will increase our understanding of the eye and how to fix it when things go wrong.