November 20, 2008
Developing a Tiny, Wireless Sensor to Monitor Glaucoma Around the Clock
Nearly 70 million people worldwide have glaucoma, an insidious group of diseases that damages the optic nerve and leads to vision loss and blindness. High intraocular pressure, which damages nerve cells in the eye, is one of the biggest known contributing factors in the development of glaucoma.
Glaucoma testing is usually administered as part of a comprehensive eye exam. If detected early enough, aggressive treatment to lower pressure can delay progression of the disease in many people. A problem with this strategy, according to Howard Hughes Medical Institute investigator Simon W. M. John at The Jackson Laboratory, is that intraocular pressure is usually only tested in the doctor's office once or twice a year at most. “This can help to discern some degree of risk,” said John. “But a person's pressure in the doctor's office may be normal, when, in fact, it might be much higher at night. On any given day, intraocular pressure can vary quite a lot.”
“This program requires the investigators to step outside of their normal comfort zone and expertise.”
Simon W. M. John
For more than a decade, John has worked to improve the power of mouse models for studying glaucoma. His group is currently using a combination of molecular, genetic, and physiologic methods to identify the genes and pathophysiologic processes that contribute to glaucoma. Using mouse models and genetics is important for understanding the neurobiology of glaucoma and the involvement of elevated intraocular pressure in the disease.
But as good as those approaches are, John feels that glaucoma researchers are in desperate need of new tools for measuring intraocular pressure in mice more frequently. With a new HHMI Collaborative Innovation Award, John has enlisted the expertise of Purdue University professors Pedro Irazoqui and William J. Chappell, to help in developing the world's first ultra-miniature pressure-sensing device that can be implanted into the eyes of mice who have - or are at risk for developing - glaucoma.
According to John, having such a device would permit scientists to monitor intraocular pressure in mice around the clock and learn more about how the disease progresses. If their device design is successful, it may be used as a prototype for a revolutionary way to monitor intraocular pressure - or even blood pressure - in humans.
The idea for developing such as device arose from John's strong conviction that his own research would benefit greatly if he could monitor intraocular pressure in his mice continuously rather than only at specific times during the day. He cites a few reasons why this would be helpful: “Right now, we only know that high pressure is harmful over time,” he said. “We don't really know whether a pressure that is high over time is worse for the eyes than a pressure that keeps spiking up and down and changing over time. And we don't yet understand what threshold of pressure is damaging and how that varies between individuals. But we don't have the means right now to make continuous pressure measurements that would help us answer these questions.”
The sensor that John, Irazoqui and Chappell are
designing will be self-powered and a little thicker than a human hair. They aim
to make it capable of measuring eye pressure automatically and transmitting
pressure data to the outside world via a tiny wireless antenna. John believes
that size matters a great deal. “If it is small enough, it might have
uses beyond glaucoma, such as monitoring blood pressure or cerebrospinal
fluid,” he notes.
With such a device in hand, John says scientists will be in a much better position to begin answering nagging questions about how glaucoma starts and how it progresses. “It could really revolutionize our mechanistic understanding of how pressure inside the eye contributes to glaucoma and neurodegeneration,” he said.
The sensor is not a new idea. John and others in his lab began sketching out designs for such a device a couple of years ago - long before the announcement of the HHMI Collaborative Innovation Awards. Despite his lab's success at creating the first method for measuring intraocular pressure in mice, his group's efforts to design a sensor small enough to implant in a mouse's eye always fell short. “We were not well equipped to do this kind of work, so those efforts never got very far,” he said.
John knew he needed additional technical expertise. Not willing to accept defeat, he kept his eyes open for potential collaborators who had the engineering and microfabrication know-how that his group was lacking. His vigilance paid off when he came across a news report in 2007 about Irazoqui, an assistant professor of biomedical engineering at Purdue University, who was already developing small sensors to implant in the eyes of people with glaucoma. “His sensors were much smaller than what other people were developing,” said John. “I thought, `Aha, here is a person who has the energy, has good ideas and is interested in the problems that I am interested in.'”
John looked up Irazoqui's phone number and called him soon after reading about his work. Irazoqui was on vacation in Spain - but he returned the call. “We had a great conversation. He was excited by my ideas and we agreed to talk further,” said John.
After several more phone conversations, John flew to Indiana to meet with Irazoqui and his close collaborator William Chappell, an associate professor of electrical and computer engineering at Purdue. Broadly speaking, Chappell `s research group focuses on applied electromagnetics. He is an expert in the design and manufacture of antennas and advanced biocompatible packaging.
“The three of us had a wonderful series of meetings - lots of energy and ideas,” said John. “By the time we had finished, we had sketched out some quite good ideas. Our collaboration was launched. What really appealed to them was not only could they see this approach as being revolutionary in biology, but it was really pushing the envelope on the engineering and the antenna designs.”
Shortly after the meetings at Purdue, John received word from HHMI that it was going to start a pilot program to fund transformative, collaborative research. It seemed a perfect match for the plans that John, Irazoqui and Chappell were drawing up. “This program requires the investigators to step outside of their normal comfort zone and expertise. We thought our plan was a good match - so we applied,” said John.