Miller School’s Innovative Diabetes Clinical Trial Transplants Pancreatic Islets into Patients’ Eyes

Diabetes researchers at the University of Miami Miller School of Medicine are taking an innovative approach to restoring insulin production in people with type 1 diabetes (T1D) — one of the most challenging aspects of treating this serious chronic disease. Currently, patients with T1D face a lifetime of daily insulin injections unless insulin-producing cells can be successfully transplanted. Transplants of the pancreas or isolated pancreatic islet cells to the liver have been performed. Both procedures typically require long-term generalized immunosuppression to avoid the graft’s rejection.

Now, Midhat Abdulreda, M.S, Ph.D., associate professor of surgery at the Diabetes Research Institute (DRI), is leading a first-of-its-kind pilot clinical trial to transplant pancreatic islet cells into the eye — an immune-privileged site that doesn’t provoke an inflammatory response like the liver. This new “intraocular transplant” partnership with Bascom Palmer Eye Institute, the Miller School’s Department of Ophthalmology, could eventually lead to better outcomes for T1D patients around the world.

“Our team at the Diabetes Research Institute is constantly looking for new approaches to help our patients and find a lasting treatment for this autoimmune disease,” said Dr. Abdulreda, who is collaborating with Sonia Yoo, M.D., professor of ophthalmology and the Greentree Hickman Chair in Ophthalmology at Bascom Palmer.

“Diabetes has become one of the most common diseases in modern society, and many patients require lifelong treatments that have side effects,” Dr. Yoo said. “We want to decrease the burden of taking medications and restore the body’s ability to produce insulin on its own.”

Although blindness can be one of the side effects of advanced diabetes, the intraocular transplant procedure aims at restoring the body’s insulin production with potential benefits to a wide range of organs and tissues.

“If this therapy is successful against diabetes, it may also benefit eye disease, neuropathy, blood vessel disorders, and other complications of diabetes,” Dr. Yoo said. “It’s an exciting approach for treating T1D.”

Extensive Preclinical Studies

When Dr. Abdulreda joined the DRI in 2007, he began investigating the body’s immune reactions to transplanting pancreatic islet cells. Currently, the islet transplant procedure involves infusing a large number of islet cells into the veins of the liver in a minimally invasive procedure. While patients typically see a significant improvement in their quality of life, the transplants often provoke an inflammatory reaction that can reduce the insulin production of the islet cells and lead to graft failure over the long term.

“The idea of transplanting islet cells to the eye was proposed more than 50 years ago,” Dr. Abdulreda said. “Since then, scientists have been intrigued by the possibility of gaining direct noninvasive access to the body through the living window of the cornea.”

In 2008, researchers at DRI and Karolinska Institutet in Sweden, led by Per-Olof Berggren, visiting professor of surgery at the DRI and director of the Rolf Luft Center for Diabetes and Endocrinology Research at Karolinska, demonstrated for the first time the reversal of diabetes after islet cell transplant in the front part of the eye in recipients who were genetically matched to the donor.

In the past decade, Dr. Abdulreda, in collaboration with colleagues at the DRI and Karolinska, has conducted extensive preclinical studies in his laboratory to determine if intraocular transplants can be effective in reversing or curing diabetes in the mismatched donor-recipient setting. He is also investigating ways to achieve this without the need for continuous immunosuppression.

“First, we considered implanting the islet cells in a capsule to avoid the immune attack,” he said. “But we learned from our experimentations that islet grafts from mismatched donors could thrive in the eye without the need for permanent immunosuppression. Our results were very promising and opened the door to this pilot clinical trial.”

Recruiting Specific Patient Profiles

After receiving approval from the U.S. Food and Drug Administration and initial funding through the Diabetes Research Institute Foundation (DRIF) and the Dr. Robert C. and Veronica Atkins Foundation, Dr. Abdulreda, Dr. Yoo, and their clinical research teams began recruiting patients for this pilot phase 1 trial to evaluate the general safety and potential efficacy of transplanting islets in the anterior chamber of the eye. The trial is currently funded through the DRIF and the Novo Nordisk Foundation in Denmark.

“We took a conservative approach and are only recruiting legally blind T1D patients between 18 and 70 with persistent, severe hypoglycemia,” Dr. Abdulreda said.

“The islets will be infused into one eye that is already blind so the participant’s vision will not be compromised,” Dr. Yoo added.

The islet cells are injected gently into the interior chamber of the eye, where they spread on the iris and quickly hook to its blood vessels.

“The high oxygen levels within the eye initially support the transplanted cells, which quickly engraft and begin sensing blood sugar levels in the blood and responding by releasing insulin as needed,” Dr. Abdulreda said.

Noting that immunosuppression medications will be used in limited doses, Dr. Abdulreda said participants simply lie down for several hours after the infusion until the new islet cells attach to the iris and they can go home.

“This is a very important clinical trial for the future of diabetes research,” he added. “We look forward to the results and the future expansion of this clinical research to leverage the many benefits intraocular islet transplant has to offer.”

For more information on the clinical trial, visit https://diabetesresearch.org/intraocular-islet-transplant/.

Tags: Bascom Palmer Eye Institute, Department of Ophthalmology, Diabetes Research Institute, Dr. Midhat Abdulreda, Dr. Per-Olof Berggren, Dr. Sonia Yoo, DRI, intraocular transplant, pancreatic islets, type 1 diabetes