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Type 1 diabetes: implanting insulin-secreting cells in the eye

 Type 1 diabetes: implanting insulin-secreting cells in the eye

Researchers at the Diabetes Research Institute (DRI) at the Miller School of Medicine at the University of Miami may have found a way to achieve immune tolerance to insulin-producing pancreatic cells in the treatment type 1 diabetes: transplant 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), researchers explain that transplanting islets of Langerhans into the eye would prevent immunosuppressive therapy. . 

Furthermore, these initial islet transplants in the recipient's eye would induce lasting peripheral immune tolerance in the recipient in the event of another transplant.

A transplantion into the anterior chamber of the eye

 Also called insulin-dependent diabetes (IDD), type 1 diabetes is an autoimmune disease characterized by excess sugar in the blood. This hyperglycemia is caused by stopping 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 sugar levels with daily insulin therapy. 

As the researchers indicate, transplanting islets of Langerhans can restore natural insulin production in people with type 1 diabetes. However, these transplant patients must also receive lifelong immunosuppressive therapy to prevent the rejection of these donor cells. Not only does prolonged use of anti-rejection drugs lead to serious side effects, but immune attack against transplanted islets of Langerhans can 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

 Researchers in the current study transplanted islets into the anterior chamber of the eye of non-human experimental and preclinical recipients.

 Another group received islets implanted in the kidney. Both groups were transiently treated with anti-CD154 / CD40L blocking antibodies during the period of transplantation. This antibody prevents the interaction between certain molecules (CD40-CD40L) on the surface of cells of the immune system which play a key role in the rejection of transplants. 

The researchers were particularly interested in this immune pathway because it is particularly promising for the transplantation of islets of Langerhans. 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 in the body.


70% of recipients survived 400 days without continuous immunosuppression 

In both groups of recipients - those who received a first islet of Langerhans transplant into the eye or kidney, as well as short-term treatment with the anti-CD154 antibody - results showed immunosuppression-free survival 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 recipients survived the second kidney transplant for more than 400 days without continued immunosuppression. By comparison, only 30% of those who received islets in the kidney survived more than 400 days without continuous immunosuppression. Further studies in the preclinical model have shown a reduction in donor specific immune reactivity in the blood, which corresponds to induced peripheral immune tolerance. "Preliminary results from these diabetes study models demonstrate the establishment of immune tolerance to transplanted islets and their long-term protection against immune attacks long after stopping anti-rejection therapy. D “Further trials in human subjects are needed to validate this approach in people with type 1 diabetes,” says Dr Midhat Abdulreda, assistant professor of surgery at DRI. "This approach could have a positive impact on the success of islets of Langerhans transplantation for the future treatment of diabetes," concludes Dr. Per-Olof Berggren, co-author of the work.


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