New technique may prevent graft rejection in high-risk corneal transplant patients

May 01, 2017
Treating donor tissue with a special cocktail of molecules improves outcomes and promotes survival of high-risk corneal transplants

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Boston, Mass. — Treating donor corneas with a cocktail of molecules prior to transplanting to a host may improve survival of grafts and, thus, outcomes in high-risk corneal transplant patients, according to a new study led by researchers at Massachusetts Eye and Ear. The findings, published online in Scientific Reports, describe a novel strategy to promote the tolerance of corneal transplants in patients at high risk for rejection by targeting antigen-presenting cells in donor tissues with a combination of two cytokines, TGF-β and IL-10, that work together 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” said senior author Reza Dana, M.D., MPH, Director of Cornea and Refractive Surgery at Mass. Eye and Ear and the Claes H. Dohlman Professor of Ophthalmology at Harvard Medical School. “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.”

With more than 150,000 cases performed each year worldwide, corneal transplantation is the most common transplant procedure in medicine. Patients may need corneal transplants when the cornea, the transparent, outermost layer of the eye, is no longer able to let light in due to scarring or disease. An ophthalmologist removes a section of the injured or diseased cornea and replaces it with donor tissue.

Many corneal transplants are successful in restoring vision to those with damage to the surface of the eye, with the help of steroids to suppress the body’s natural immune response to reject the donor tissue; however, roughly one-third of all cases are considered “high-risk,” with increased chance of rejecting even with the use of steroids to suppress the immune system. These patients often show signs of a degeneration of what is known as T cell-immunity.

With the goal of improving survival of cornea grafts for patients in the high-risk category, the authors of the Scientific Reports study developed a 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 team accomplished this by treating donor tissue with the TGF-β and IL-10 cocktail, and then grafting them onto high-risk recipient eyes of a preclinical model. Eight weeks post-transplantation, they noted a significant increase in graft survival (68.7 percent of treated grafts had survived, while none of the control grafts had survived).

The researchers are hopeful that this novel method of using a combination of cytokines working together to promote tolerance of corneal grafts — by treating the donor tissue rather than the recipient — 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,” said Dr. Dana. “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.”


In addition to Dr. Dana, authors on the
Scientific Reports paper include Maryam Tahvildari, M.D., Parisa Emami-Naeini, M.D., MPH, Masahiro Omoto, M.D., Ph.D., Alireza Mashaghi, M.D., Ph.D., and Sunil K. Chauhan, Ph.D, of Schepens Eye Research Institute of Mass. Eye and Ear.

This research study was supported by National Institutes of Health/National Eye Institute grants R01EY12963, T32EY007145 and P30EY003790.

About Massachusetts Eye and Ear 
Mass. Eye and Ear clinicians and scientists are driven by a mission to find cures for blindness, deafness and diseases of the head and neck. Now united with Schepens Eye Research Institute, Mass. Eye and Ear is the world's largest vision and hearing research center, developing new treatments and cures through discovery and innovation. Mass. Eye and Ear is a Harvard Medical School teaching hospital and trains future medical leaders in ophthalmology and otolaryngology, through residency as well as clinical and research fellowships. Internationally acclaimed since its founding in 1824, Mass. Eye and Ear employs full-time, board-certified physicians who offer high-quality and affordable specialty care that ranges from the routine to the very complex. In the 2016–2017 “Best Hospitals Survey,” U.S. News & World Report ranked Mass. Eye and Ear #1 in the nation for ear, nose and throat care and #1 in New England for eye care. For more information about life-changing care and research, or to learn how you can help, please visit MassEyeAndEar.org.

About the Harvard Medical School Department of Ophthalmology
The Harvard Medical School (HMS) Department of Ophthalmology (eye.hms.harvard.edu) is one of the leading and largest academic departments of ophthalmology in the nation. More than 350 full-time faculty and trainees work at nine HMS affiliate institutions, including Massachusetts Eye and Ear, Massachusetts General Hospital, Brigham and Women’s Hospital, Boston Children’s Hospital, Beth Israel Deaconess Medical Center, Joslin Diabetes Center/Beetham Eye Institute, Veterans Affairs Boston Healthcare System, VA Maine Healthcare System, and Cambridge Health Alliance. Formally established in 1871, the department has been built upon a strong and rich foundation in medical education, research, and clinical care. Through the years, faculty and alumni have profoundly influenced ophthalmic science, medicine, and literature—helping to transform the field of ophthalmology from a branch of surgery into an independent medical specialty at the forefront of science.