The image of research as “an ivory tower housing statistics and microscopes,” is a popular one. While basic research has traditionally been far removed from patient clinics, translational research is bridging the gap getting breakthrough discoveries to patients faster that ever.
Translational Research is a new initiative of the National Institutes of Health (NIH). It seeks to “translate” basic research discoveries into patient care by encouraging collaborations between basic scientists and clinicians. At the Havener Eye Institute, our physicians are taking it one step further by identifying patient care problems and initiating research themselves based on real-world problems.
MAKING A DIFFERENCE
Retinal detachment (a condition where the light sensitive tissue inside the eye becomes separated from the back of the eye) can be a potentially blinding condition. The worst outcomes are in those patients who develop scar tissue in the retina, called proliferative vitreoretinopathy (PVR).
“My research is focused on clinical problems,” said OSU's Colleen Cebulla, MD, PhD. “As a retina surgeon, I see patients that are affected by retinal detachments. We want to help them regain their vision either by promoting regeneration of damaged retinal tissue or eliminating scar tissue formation."
Retinal damage and scarring problem are not isolated to retinal detachment patients. Patients with macular degeneration, diabetes, ocular trauma, some infections, and other retinal conditions can also have scarring. Depending on where the scars form they can interfere with vision. By understanding how scarring develops, Dr. Cebulla hopes to be able to inhibit it in critical vision areas.
While there are many theories on PVR prevention, in practice the theories have not really held up. Not knowing the critical proteins that promote the scarring process and how to target them is a part of the problem. Dr. Cebulla believes that if we knew the target proteins, we could develop better medication to prevent or reduce the scarring as well as try to promote healing of damaged retinal tissue.
Her first step was to compare the proteins that are increased or involved in a PVR retina with a normal retina in animal models.
“I did what’s called iTRAQ labeling of the proteins,” explained Dr. Cebulla. “A tag is added to a protein so the mass spectrometer machine can recognize it. This can tell me if a protein has increased or decreased in a PVR retina sample compared to a normal retina sample. I found 567 extra proteins and am very interested in which are the most important targets to study and trying to develop therapeutics.”
Once the targets are identified in the animal model, Dr. Cebulla will conduct similar studies with human PVR retina. This will help identify the target proteins involved in scarring and regeneration. Medication that inhibits these proteins can then be tested and with success will lead to clinical trials.
“I see problems every day that affect people,” said Dr. Cebulla. “It makes me want to go to the lab and find new treatments that will help my patients and patients everywhere.”
Anti-Vascular Endothelial Growth Factor (anti-VEGF) medications such as Avastin® and Lucentis® inhibit the growth of new blood vessels. This is important for patients with several common retina conditions, but might have adverse effects on other parts of the body that are trying to heal.
“It's a basic question. We give our patients anti-VEGF medication in the eye,” said John Christoforidis, MD. “How do we know that it stays in the eye?”
Dr. Christoforidis decided to do more than ask the pharmacokinetic (the study of what happens to a drug once it is administered) question. He met with other retina specialists to discuss strategies for tracking the dispersion of anti-VEGF medication once injected.
Dr. Christoforidis then consulted his brother, a radiologist, to discussed gadolinium, a dye used in imaging. He learned that gadolinium is not very useful for longterm imaging because after a few days it blends in with the surrounding tissue. Radiolabeling, a process using radioactive isotopes (a decaying chemical element that is easy to track) as tracers would be better. Rather than contacting a research scientist, Dr. Christoforidis took matters into his own hands.
So, is that small amount enough to inhibit wound healing? This question prompted an additional research project into what effect the small amount of anti-VEGF would have. Dr. Christoforidis found that even the small amount that enters the bloodstream is statistically significant in inhibiting wound healing.
“This result can be instantly translated to the clinic,” said Dr. Christoforidis. “If I have a patient in the clinic that is considering surgery or has an open wound, I now know to suspend the anti-VEGF medication and consider alternative treatments.”
A secondary finding of his radiolabeling project was that Dr. Christoforidis obtained comparable results much faster than other more extensive, long-term pharmacokinetic studies. Also, he was also able to use a single animal subject multiple times, while the larger studies used many more animals to get the same results. This discovery is exciting in itself because it establishes a better method for tracking the pharmacokinetics of medications.
DISCOVERIES INTO TREATMENT
With the immense research resources available at Ohio State and the willingness for collaboration between departments, clinical questions can be answered in the lab and start benefiting our patients in the clinic faster than ever before.
“We take questions from the clinic to the lab and bring the answers back to the clinic,” said Dr. Christoforidis. “We do it for the patients that we see every day.”
“There is something to be said for the thrill of discovery,” said Dr. Cebulla, “It’s always kind of exciting, like a puzzle that you work out. But, what really motivates me most, is the hope that a discovery we make today will be able to really help our patients.”