US research highlights a new approach for the treatment of type 1 diabetes: transplantation into the eye of pancreatic insulin-producing cells. This technique would not only prevent continued immunosuppression, but could even lead to long-term peripheral immune tolerance in other transplant sites.
Researchers at the University of Miami's Miller School of Medicine's Institute for Diabetes Research (DRI) may have found a way to achieve immune tolerance to insulin-producing pancreatic cells in the treatment of type 1 diabetes: transplanting them into the eye.
In an article published online in the journal Diabetologia, the journal of the European Association for the Study of Diabetes (EASD), the researchers explain that islet transplantation Langerhans in the eye would avoid immunosuppressive treatment. In addition, these initial islet transplants in the recipient's eye would result in a durable peripheral immune tolerance in the recipient in case of another transplant.
A transplant in the anterior chamber of the eye
Also known as insulin-dependent diabetes mellitus (IDDM), type 1 diabetes is an autoimmune disease characterized by an excess of sugar in the blood. This hyperglycemia is due to the cessation of the production of insulin, a hormone secreted by pancreatic islet cells called islets of Langerhans. In type 1 diabetes, these insulin-producing cells have been mistakenly destroyed by the immune system, forcing patients to manage their blood glucose levels through daily insulin treatment.
As the researchers say, islet transplantation helps restore the natural production of insulin in people with type 1 diabetes. However, these transplant patients must also receive immunosuppressive treatment for life to prevent the rejection of these donor cells. Not only does prolonged use of anti-rejection drugs lead to serious side effects, but the immune attack against transplanted islets of Langerhans may still occur despite treatment. Finding a way to reduce or eliminate the need for immunosuppressive therapy is therefore one of the main challenges of type 1 diabetes research.
Implantation in the anterior chamber of the eye
The researchers in this study transplanted islets into the anterior chamber of the eye of experimental and non-human preclinical recipients. Another group received islets implanted in the kidney. Both groups were transiently treated with anti-CD154 / CD40L blocking antibodies during the time of transplantation. This antibody prevents the interaction of certain molecules (CD40-CD40L) on the surface of the cells of the immune system that play a key role in graft rejection. Researchers have been particularly interested in this immune pathway because it is particularly promising for islet transplantation.
After performing the first transplants and administering the antibody treatment, the team then transplanted other islets of Langerhans into the kidney of the experimental group of recipients to assess any potential effect on immune tolerance at another site of the body.
70% of recipients survived 400 days without continued immunosuppression
In both groups of recipients - those who received a first islet transplant of Langerhans in the eye or kidney, as well as short-term treatment with anti-CD154 antibody - the results showed a survival without immunosuppression for more than 300 days. This is particularly the case for the group that initially received a pancreatic islet transplant in the eye: over 70% of the recipients survived the second kidney transplant for more than 400 days without continued immunosuppression.
In comparison, only 30% of those who received islets in the kidney survived more than 400 days without continued immunosuppression. Other studies in the preclinical model have shown a reduction in the donor's specific immune reactivity in the blood, which corresponds to an induced peripheral immune tolerance.
"The preliminary results of these diabetes study models demonstrate the establishment of immune tolerance to transplanted islets and their long-term protection against immune attack long after stopping anti-rejection therapy. "Other trials in humans are needed to validate this approach in people with type 1 diabetes," says Dr. Midhat Abdulreda, assistant professor of surgery at the DRI.
"This approach could have a positive impact on the success of islet transplantation for the future treatment of diabetes," concludes Dr. Per-Olof Berggren, co-author of the work.