Researchers hold greater hope for the success of secondary corneal transplants, which to date have been rejected at triple the rate of first-time corneal transplants.
In Australia more than 2000 transplants are performed each year and in the United States more than 40,000 transplants are performed annually to replace the cornea with tissue from a donor. According to the American Academy of Ophthalmology, most corneal transplants are done to correct severe visual impairments caused by keratoconus, a condition in which the normally dome-shaped cornea progressively thins and becomes cone-shaped.
Ninety per cent of first-time corneal transplants are successfully performed without matching donor tissue to that of the recipient, due to immune privilege. In patients requiring a second transplant, just
30 per cent are a success.
Dr. Jerry Niederkorn, Professor and Vice Chair of Research of Ophthalmology and senior author at University of Texas Southwestern Medical Center said, “We believe that this loss of immune privilege is similar to an alarm that signals the immune system of potential infection, which results in a full blown immune response at the expense of the corneal transplant”.
Researchers studying mouse models discovered that after the first corneal transplant is accepted, T regulatory cells prevent other types of immune cells from attacking and rejecting the transplant. But severing corneal nerves, which occurs during the first transplantation procedure, releases high levels of the neuropeptide Substance P. The resulting high Substance P levels disable the T regulatory cells needed for acceptance of subsequent corneal transplants. This inactivation results in rejection of more than 90 per cent of the second corneal transplants in mice and helps to explain the curiously high risk for corneal graft rejection in patients who receive a second corneal transplant.
Researchers found that the high Substance P levels can be blocked with drugs to restore the eye’s immune privilege and promote the acceptance of second corneal transplants.
Professor Gerard Sutton, Sydney Medical School Foundation Chair of Cornea and Refractive Surgery, said the study was “very interesting” although it was “important to be careful when extrapolating from an animal model to human”. He said depending on the indication for surgery, up to 50 per cent of transplant patients go on to have a second transplant and that the Australian Corneal Graft Registry clearly shows that second grafts have higher risk of rejection and failure in general.
“This study proposes that it is the induced neuropathy that primes the host for rejection of the second transplant… The elevated substance P may well be a factor but transplant rejection is a complex process. The proof of the pudding would be showing that a down regulation of substance P would indeed increase graft survival in second transplants,” said Professor Sutton.
