Purdue University student’s research project related to zebrafish eye
development could lead to a better understanding of vision problems that
affect billions of people worldwide.
Li, as an undergraduate student in biological sciences, led a research
team that uncovered an enzyme’s role in the regulation of eye size in
the fish. If the enzyme’s role is similar in human eyes, it could be
relevant to human vision problems, such as nearsightedness and
insights into the process of eye-size control in zebrafish may help our
understanding of the regulation of eye size in humans,” said Li, who
has since graduated and is pursuing a doctorate in neuroscience at
Washington University. “Vision problems occur when the size or shape of
the eye changes, and what causes this is unclear. Perhaps this research
will lead to a better understanding of this mechanism and the discovery
of a new treatment for these problems.”
vision problems, called refractive errors, occur because the physical
length of the eye from the cornea to the retina is different from the
optical length. If an eye is too long or too short, light is focused in
front of or behind the retina and vision is blurred, she said.
Refractive errors affect 3.8 billion people worldwide, according to the International Center for Eye Education.
worked in the laboratory of Yuk Fai Leung, a Purdue assistant professor
of biological sciences. Leung oversaw the research and guided the team,
but credits the two undergraduate students in his lab for the idea.
inspiration for this study came from the undergraduate students,” he
said. “Their observations and interpretations helped shape our current
focus and allowed us to make this discovery. I’m very proud of the
scientists they are becoming.”
findings are detailed in a paper in PLoS ONE. In addition to Li and
Leung, paper co-authors include Purdue undergraduate student Devon Ptak,
postdoctoral researchers Liyun Zhang and Wenxuan Zhong, and continuing
lecturer Elwood Walls.
are used as a model to study development and growth problems. The
zebrafish, which are named for their naturally occurring black stripes,
must be made transparent to enable the careful observation and imaging
necessary for the research. The most common way to achieve this
transparency is to treat zebrafish embryos with a chemical called
phenylthiourea that blocks the formation of black pigment, he said.
had previously observed that zebrafish embryos treated with the
chemical have smaller eyes than untreated fish, and found that in
addition to blocking pigmentation, the chemical inhibits thyroid
thyroid produces hormones that regulate metabolism and influence
growth, and it was thought that a general suppression of the thyroid
hormone could be causing the reduction in eye size. Li theorized that
phenylthiourea might suppress thyroid hormone production because it
shares the same structure as a known thyroid hormone inhibitor. She
tested the effects of several different inhibitors and found that not
all had the same effect on eye growth. Only those that halted production
of the enzyme thyroid peroxidase resulted in smaller eye size.
thyroid peroxidase has a specific role in the regulation of eye growth,
it would be logical for it to express in the eye,” Leung said. “Perhaps
a localized manipulation of its activity in the eye could be used as a
strategy to correct some vision problems. Of course, first we must learn
much more about how it regulates eye size.”
findings also serve as a warning of the potential changes
phenylthiourea may have on zebrafish – a widely used animal model – that
could affect research results, he said.
findings and others have shown that phenylthiourea can affect various
aspects of physiology, so the results obtained from fish treated with it
may not truly reflect what is going on inside the embryo,” Leung said.
“One should be cautious in interpreting their findings after
phenylthiourea treatment. This discovery highlights the need to find a
new way to remove pigmentation.”
group attempted to find an alternative inhibitor for pigmentation, but
all caused physiological problems and none were as efficient as
phenylthiourea, he said.
The team plans to further investigate the relationship of thyroid peroxidase and thyroid hormone on eye growth and development.
said the team also is analyzing the effects of traditional Chinese
medicines considered good for vision using fish models of human retinal
“Hopefully our efforts will expedite the discovery of novel treatments for human eye diseases,” he said.
and Ptak received national Sigma Xi awards for vision research. Li also
was a recipient of a Sandy and Zippy Ostroy Research Experience for
Undergraduates Award and a Dr. William H. Phillips Undergraduate
Research Internship. In addition to those awards, this research was
funded by grants from the National Science Foundation and U.S.
Department of Energy.
Source: Purdue University