SEEING EYE DOCS
All eyes are turning toward the new Doheny Retina Institute, where scientists have launched an all-out crusade against blinding diseases.
Eugene de Juan, Jr., M.D., sounds like a modern-day Christopher Columbus when he describes his vision of the future of ophthalmology. “The world isn’t flat,” he says. “It’s round; it’s multi-dimensional. There are many new and unique ways to approach both research and patient care, things nobody has tried before. Until now. Now, we’re going to try them here.”
“Here” is the Keck School of Medicine of USC. “Here” is the Doheny Eye Institute. “Here” is the Doheny Retina Institute, his latest endeavor, which has a mission of bringing “first new hope, then relief and answers” to patients with retinal disease. The Doheny Retina Institute, explains de Juan, will focus on the type of translational research typical of USC, while breaking new ground in the treatment of some of ophthalmology’s toughest maladies.
De Juan joined the Keck School in August as a professor of ophthalmology. He was recruited along with his colleague Mark Humayun, M.D., Ph.D., also a professor of ophthalmology at the Keck School, and four of their team members from the Wilmer Eye Institute at the Johns Hopkins University School of Medicine. Those team members are: assistant professors of ophthalmology Mahmoud Mahmoud, M.D., Ph.D., Signe Varner, Ph.D., James Weiland, Ph.D. and Aaron Barnes, instructor of ophthalmology.
De Juan, Humayun and their colleagues are internationally recognized as pioneers in many areas of vision research and treatment. They are perhaps best known for the invention and development of an intraocular retinal prosthesis, or “eye chip,” which may be able to restore sight to people with degenerative diseases of the retina such as retinitis pigmentosa and age-related macular degeneration.
“We came to USC because we found Doheny and the university to be very forward-thinking and flexible,” says Humayun. “Because of this, it has a unique environment for medical research and the application of that research to develop new products and services for patients. In particular, the Doheny Eye Institute and the Alfred E. Mann Institute for Biomedical Research provide an unparalleled combination that will help the Doheny Retina Institute to develop new therapies for eye diseases and in particular retinal diseases.”
Creative culture
What de Juan and Humayun are planning to do at the Doheny Retina Institute—integrate research and development of products for clinical use—has never been done successfully before in this field, according to de Juan. “The Doheny Retina Institute is going to be a unique structure,” he says. “It is bringing under one roof all of the components involved—from discovery to development to application and commercialization of new ideas and treatments and products and services—to enhance the care of patients.”
The Doheny Retina Institute’s leadership consists of de Juan, chief executive officer, Humayun, associate director of research, Lawrence Chong, M.D., chief operating officer of the retina clinic, and Jennifer Lim, M.D., director of clinical trials. In the short term, they want to rapidly develop new treatments, products and services for patients with severe retinal disease, and to concentrate on achieving a 50 percent reduction in the vision loss associated with age-related macular degeneration (AMD). Over the long term, they want to develop therapies that can actually prevent AMD from getting started.
To reach the level of creativity necessary to achieve these goals the Institute will be shaped as a university research institute with a corporate flair. “We’re going to use a business model to help us,” says de Juan. “We will set measurable goals and gauge our progress on the achievement of these goals. It’s a radically different culture than is usually found in a university setting, but I believe it’s going to be successful.”
The advantage of this model, says de Juan, is that the problem at hand is being addressed not only by the talents of the institute staff, but by the talents of the existing USC staff, a network of philanthropists eager to advance the cause of medicine, an extensive university infrastructure that includes such hospital partners as USC University Hospital, and medical school students enthusiastic to get involved with state-of-the-art research.
“There’s no reason for smart people to work on things someone else has already figured out,” de Juan notes. “At the Doheny Retina Institute, by the time students graduate, they will have participated in ‘the real thing’—done research where the answers are needed and maybe even developed products that help patients.”
Revolutionary initiatives
The addition of de Juan and Humayun to the Keck School of Medicine and the Doheny Eye Institute will open new avenues of research and treatment for retinal disease, says Stephen J. Ryan, M.D., dean of the Keck School. In addition to Doheny, Ryan cites USC University Hospital for supporting the recruitment of the team and building modern operating rooms to advance patient care. “I have every confidence that Gene and Mark and their team will fundamentally change our field and improve the outlook for patients with retinal disease throughout the world.”
Adds Ronald E. Smith, M.D., chair of ophthalmology, “The recruitment of these physicians combined with our existing excellent retina faculty—Tom Chang, Lawrence Chong, Christine Flaxel, and Jennifer Lim—gives us the critical mass of first-rate clinicians and scientists needed to rapidly advance new treatments for blinding retinal diseases from the laboratory to patients.”
De Juan places the credit on the “foresight, courage and leadership of Dean Ryan and Dr. Smith—along with Doheny and USC—to entrust us with the responsibility and give us the freedom to concentrate these resources so these goals can be achieved.”
De Juan received his master’s degree in biochemistry from the University of Alabama in Birmingham, and his M.D. from the University of South Alabama College of Medicine, where he also did his internship training. He arrived at the Hopkins Wilmer Eye Institute in 1980 as a resident and went on to do a fellowship in vitreoretinal surgery at Duke University. He returned to Hopkins to start up the Microsurgery Advanced Design Laboratory, or MADLAB. The team assembled in that lab, most of whom have joined de Juan at USC, have been responsible for more than 100 inventions over the past nine years. Among them was the development of a new microsurgical technique known as macular translocation that, de Juan says, “is the only treatment that currently can improve vision in patients with macular degeneration.”
The Food and Drug Administration has approved another MADLAB innovation —what de Juan calls a “revolutionary new procedure that is the ultimate in minimally invasive surgery.” It is a surgical system that uses a miniaturized trochar (a pointed, hollow cylinder) and other, similarly shrunken tools half the size of those that came before them.
This system—called the TSV25, or 25-gauge transconjunctival standard vitrectomy surgical system—is used in vitreoretinal surgery, any surgery that involves the retina or the fluid-filled chamber that lies between the retina and the lens. These miniature instruments, says de Juan, allow a surgeon to reach the retina without cutting into the eyeball. “We just go in with this little, tiny needle,” he explains. And no cutting means no suturing. “It’s just like when you draw blood; the natural elasticity in the tissue quickly closes the hole. This shortens the closing time of these operations by 50 percent or more.” It also significantly reduces the amount of anesthesia necessary.
The TSV25, brought to the market by Bausch & Lomb, will be the smallest minimally invasive surgical system ever commercialized in the United States, says de Juan. And it is so versatile that it can be used in about 80 percent of the 200,000 vitreoretinal surgeries performed in this country each year—surgeries to remove hemorrhages and scar tissue and to treat diabetic retinopathy, retinal detachment, retinal holes and even macular degeneration.
Adds de Juan, who already holds 22 patents, there are many more advances to come from within the MADLAB and the Doheny Retina Institute. For example, the Institute’s scientists are pursuing two new initiatives for treatment of the wet form of AMD—the less common, but more vicious form of macular degeneration. One involves injection of an anti-angiogenesis compound into the eye to prevent the overgrowth of blood vessels that can occur with AMD; the other examines an oral medication that inhibits scar tissue formation in the macula. Both are currently being investigated only at the Doheny Retina Institute and may soon enter clinical trials.
Sight for the blind
Mark Humayun comes from a family of physicians, including his mother and four of his uncles. He received his M.D. from Duke University, where he first met de Juan. There the two began talking about engineering a prosthesis for people with degenerative diseases of the retina.
Humayun received a Ph.D. in biomedical engineering from the University of Chapel Hill in North Carolina, served a residency in ophthalmology at the Duke University Eye Center, and was a vitreoretinal fellow at the Johns Hopkins Wilmer Eye Institute.
At Hopkins, Humayun and de Juan teamed up to create their intraocular retinal prosthesis, which uses advanced microelectronics to give sight back to some of the blind. A tiny silicon chip takes the place of the damaged macula—the center of the retina, where most of the detail work of vision is done. The chip receives video input from a pair of specially outfitted glasses, and stimulates the still-viable optic nerve. The brain uses this information to create a crude but definite visual image.
To date, Humayun and de Juan have done preliminary tests on 17 blind patients with retinitis pigmentosa or macular degeneration. “These were short-term studies,” explains Humayun. “We used external electronics, and then removed everything at the end of the test.” Nonetheless, these blind patients were able to see image patterns when the microelectronic prosthesis stimulated the remaining retinal neurons.
FDA approval is expected soon for the first phase of clinical trials to implant the chips permanently on a small number of patients. The prosthesis is being manufactured by the Los Angeles-based Second Sight, founded by Alfred E. Mann, a USC Life Trustee and chairman of the board of the Alfred E. Mann Institute for Biomedical Research at USC.
While the eye chip is one path to bringing sight to the blind, Humayun is investigating a “natural” alternative—a protein derived from spinach. The protein, called Photosystem 1 or PS1, works in photosynthesis, using energy from the sun to convert carbon dioxide and water into carbohydrates. What makes PS1 perfect for use in the eye, says Humayun, is that it releases an electrical charge each time it captures a photon of light.
“It’s like a little solar cell,” he says, “but it’s organic. And it’s robust—you can isolate it, dry it for months, put metal on it, and it still does its job.”
The hope, he continues, is that it might be able to do that job within the human eye, once inserted into cell membranes in the eye. “Since the light-sensing cells are gone in diseases like retinitis pigmentosa and AMD,” he says, “the question is whether we can make the remaining cells light sensitive.”
The work is the brainchild of Eli Greenbaum, Ph.D., from the Department of Energy’s Oak Ridge National Laboratory. Experiments by Greenbaum and his team—which includes Humayun—have shown that PS1 can generate up to one volt of electricity when the protein captures a photon of light. And it is possible to deliver PS1 to cells by packaging it in a liposome—a sphere made of fat and water that acts as a sort of artificial membrane and mimics the membranes found in a living cell. “The trick is going to be how to orient the protein within the membrane so that it works properly,” Humayun says, “and how to get the cells to accept the protein as part of their own membrane and not engulf and destroy it as foreign.
“If you can do this, you won’t need all the electronics that are currently needed with a retinal prosthesis. It would be a great alternative.”
De Juan and Humayun’s vision for the Doheny Retina Institute means pursuing all possibilities. The way to achieve such a mindset, says de Juan, is to be surrounded with scientists whose minds remain open, who are also willing to explore.
“I want this to be the place to which the smartest, brightest, most energetic people are attracted,” he says.
To many, it already is.
For more information about the Doheny Retina Institute at the Doheny Eye Institute, or to learn more about The Doctors of USC, call 1-800-USC-CARE (1-800-872-2273).
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