A new strategy may increase the tolerance of corneal transplants in patients at high risk for rejection.
Researchers from Massachusetts Eye and Ear have presented a new study that shows that by targeting antigen-presenting cells in donor tissues with a combination of two cytokines, TGF-β and IL-10 can work to promote tolerance of the graft by the transplant recipient’s immune system.
“We made use of cytokines that can change the function of immune cells to induce tolerance in donor corneas,” senior author Dr. Reza Dana, director of Cornea and Refractive Surgery at Mass. Eye and Ear and the Claes H. Dohlman Professor of Ophthalmology at Harvard Medical School, said in a statement.
“We exposed donor tissue to a particular cocktail of immunoregulatory cytokines, and we’ve determined what doses, concentrations and exposure we need for these cytokines to generate tolerance inducing antigen-presenting cells in the cornea,” he added.
The researchers developed the technique in preclinical models to make the donor tissue more likely to be accepted by the host, rather than tweaking the immune system of the host to accept the donated tissue.
The researchers treated donor tissue with the TGF-β and IL-10 mixture and then grafted them onto high-risk recipient eyes of a preclinical model. After eight weeks’ post-transplant, the researchers saw that 68.7 percent of treated grafts had survived, while none of the control grafts had survived.
There are more than 150,000 cases of corneal transplantation performed worldwide each year. The transplants are necessary when the cornea is no longer able to let light in due to scarring or disease.
While many of these transplants are successful in restoring vision, about one-third of all cases are considered high-risk with an increased chance of rejecting even with the use of steroids to suppress the immune system.
The patients who reject the transplant often show signs of a degeneration of what is known as T cell-immunity.
According to the researchers, the new method along with a combination of cytokines could work towards promoting tolerance of corneal grafts and may transition more easily to the clinical setting.
“By exposing the transplant tissue to these cytokines, we avoid having to expose the transplant recipients themselves to any immunosuppressive,” Dana said. “We’re very excited, because it’s highly translatable technology.
“When we grafted the tissue that has been treated that way, we developed active tolerance, which leads to long-term acceptance of the corneal transplant and suppresses all the destructive sides of immunity,” he added.
The study was published in Scientific Reports.
Filed Under: Drug Discovery