Not in the eyebrow, but in the eye
Researchers at the Institute for the Study of Diabetes, part of the University of Miami, have proposed an alternative method for achieving immune tolerance of the body to transplanted donor insulin-producing islets in type 1 diabetes mellitus. As part of the work led by Associate Professor Midhat Abdulreda, they demonstrated that the islets transplanted into the anterior chamber of the recipient's eye are able to provide long-term tolerance of the body to the donor material.
In type 1 diabetes mellitus, insulin-producing beta cells of the pancreatic islets are destroyed by their own immune system, as a result of which patients are forced to maintain blood glucose levels with daily insulin injections. Transplantation of donor islets restores insulin production in such patients, but they need immunosuppressive therapy throughout their lives to prevent rejection of donor cells. The drugs used in this case are very toxic and do not provide complete suppression of the mechanisms of immune rejection.
In search of an alternative method to solve this problem, the authors have developed a fundamentally new approach to the transplantation of donor islets. They implanted them into the anterior chamber of the eye of mice and baboons with simulated diabetes mellitus. Islets were implanted into the kidney in the control group of animals. Both groups in the near-transplantation period (the last time on the 7th day after transplantation) received transient therapy with blocking antibodies to CD40L(CD154) molecules. These antibodies prevent the interaction between CD40L and their ligands, which are expressed on the surface of immune cells and play a key role in the mechanism of immune rejection. This immune mechanism was chosen as a target, since it is the most promising from the point of view of transplantation of insulin-producing islets.
Sequential images of mouse eyes after transplantation of incompatible allogeneic (donor) insulin-producing islets. On the left – the condition of the eye without therapy on days 7 and 24 after transplantation, on the right – the results of therapy with monoclonal antibodies to CD154 on days 7 to 347.
After primary transplantation and antibody therapy, the authors implanted an additional dose of islets into the kidneys of animals of both control and experimental groups, which allowed them to assess the potential effect of the method on immune tolerance in other regions of the body.
In the groups of recipients who underwent primary islet transplantation into the eye or kidney, as well as short-term therapy with CD154 antibodies, the duration of islet survival without immunosuppressive therapy exceeded 300 days. Moreover, in the absence of immunosuppression, the survival rate of islets implanted in the kidney of animals that had previously undergone eye transplantation exceeded 400 days in more than 70% of cases, whereas in the control groups this indicator was only 30%. Additional studies on preclinical models have demonstrated reduced donor-specific reactivity of recipient blood cells, which confirms the induction of immune tolerance.
The authors are currently evaluating the safety and efficacy of intraocular transplantation of insulin-producing islets in a phase 1 clinical trial. They hope that the results obtained in the future will allow to expand the use of islet transplantation in clinical practice.
Article by Midhat H. Abdulreda et al. Operational immune tolerance towards transplanted allogeneic pancreatic islets in mice and a non-human primate is published in the journal Diabetologia.
Evgenia Ryabtseva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of Diabetes Research Institute Foundation: Sap the eye help achieve transplant tolerance in type 1 diabetes?