A fish that can be found in almost any pet store may hold the key to therapies that can restore damaged vision and hearing in humans. Like other species of non-mammalian vertebrates, the zebrafish (Danio rerio) has the ability to regenerate cells responsible for vision and hearing, sometimes in as little as a few days.
The freshwater fish has been the subject of a long-term research project by Jonathan Matsui, who joined the Pomona faculty two years ago as an assistant professor of biology and neuroscience. Last year, he received a $440,159 National Institutes of Health (NIH) grant for the project.
Aging, poor genetics and environmental stresses caused by listening to an iPod too loudly for too long can cause our sensory hair cells in the inner ear to die, leading to irreversible deafness or difficulties with balance. Cells in the human retina are subject to similar degeneration, causing diminished eyesight or blindness. Unfortunately, unlike fish, frogs and birds, we do not have the ability to regenerate these sensory receptors.
We do, however, share certain similarities with the zebrafish, which makes it an ideal model for research on degeneration and regeneration of sensory systems, says Matsui. Although the fish doesn’t have a cochlea, which is the auditory portion of our inner ear, they do have a vestibular (balance) system which is almost identical to humans. The retina is also almost the same, adds Matsui.
The NIH grant funds research into mutant zebrafish lines that have smaller eyes due to reduced cellular proliferation in the ciliary marginal zone, a part of the retina that produces precursor cells, which can become all of the other types of cells found in the growing retina. Similarly, the inner ear of the fish has “supporting cells,” which are the source for new sensory hair cells. For Matsui, “this raises the question of whether there is a redundancy between sensory systems.”
“If the role of supporting cells in the ear is comparable to that of the ciliary marginal zone in the retina, do these mutant fish have defects in their sensory hair cell development and/or regenerative abilities?” asks Matsui. “Preliminary data indicates that these mutants have fewer hair cells. Funds from the grant will help us further characterize these fish and identify the genes causing the small eye phenomenon.” Understanding the genetics of cell proliferation in non-mammalian vertebrates could ultimately lead to therapies to restore lost hearing and vision in humans by revealing genes that regulate cells found in the eye and ear.
Matsui, whose interest in studying sensory systems started in high school, continued his research as an undergraduate at the University of Washington, where he worked in one of the laboratories that discovered it was possible for chickens to regenerate sensory hair cells in the inner ear. During his postdoctoral fellowship at Harvard University, Matsui began to focus on zebrafish to see if he could find commonalities between vision and hearing.
Matsui developed more than a research interest at Harvard. As the faculty advisor for students majoring in neurobiology, he discovered he enjoyed working with undergraduates, which he says is the main reason he chose to teach at Pomona. In his lab at Seaver South, he works with a cohort of students during the summer and throughout the academic year. This past summer, two students focused on research funded by the NIH grant, while another four students did related research on topics that included the effects of ethanol on the development of sensory systems (fetal alcohol syndrome) and genetic causes of degeneration of vision and hearing.
“I like the students’ enthusiasm,” says Matsui, “and seeing that spark when they find something that they hadn’t thought about or, possibly, when they realize that maybe it’s something that no one else in the world has ever seen before.”