Treating corneal grafts with a cocktail of cytokines prior to implantation may free transplant patients from the burden of immunosuppressive therapy, according to preclinical findings by a Massachusetts Eye and Ear research team.
The study, published in Scientific Reports, investigated outcomes of corneal transplants in mouse eyes with a high-risk for graft rejection (inflamed and vascularized graft beds) after the donor tissue was pretreated with a combination of recombinant interleukin (IL)-10 and transforming growth factor (TGF)-β.
"We made use of cytokines that can change the function of immune cells to induce tolerance in donor corneas" said senior author Reza Dana, MD, MPH, director of cornea and refractive surgery at Mass. Eye and Ear. "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."
The mouse corneas were examined in vivo for 8 weeks post-transplantation, during which the authors observed a significant increase in graft survival: 67% of cytokine-treated grafts survived compared with 0% of the saline-treated controls (P<0.0001).
For comparison, high-risk human corneal transplant recipients typically show survival rates of 50% or less after treatment with corticosteroids. And unfortunately, approximately a third of all cases fall into this high-risk category.
In a series of experiments, the team demonstrated that exposure to IL-10 and TGF-β induces the antigen presenting cells (APCs) within the donor tissue to mature into what are called tolerogenic APCs. These cells are resistant to further maturation and can induce host tolerance due to their diminished antigen presentation, production of regulatory cytokines and generation and expansion of IL-10-producing regulatory T cells.
If applied in people, this protocol could change the transplant paradigm—and may be as simple as adding the cytokines into the medium in which the donor tissue is stored and transported prior to implantation.
"By exposing the transplant tissue to these cytokines, we avoid having to expose the transplant recipients themselves to any immunosuppressive," said Dr. Dana. "We're very excited, because it's highly translatable technology."