Novel gene therapeutic strategies for the induction of tolerance in cornea transplantation.

With more than 100,000 procedures each year, corneal transplantation (keratoplasty) is the most frequent transplantation procedure in humans. Technical advances in microsurgery have moved forward to transplant isolated layers of the cornea; however, immune-mediated allograft rejection is still a key problem and continued therapeutic efforts are required to improve the prognosis of keratoplasty. New treatment protocols need to be introduced to prevent the rejection of allogeneic grafts. The genetic modification of the graft or cells prior to transplantation is an attractive approach to protect the graft from allogeneic rejection. The transplant setting offers the unique advantage for gene therapy to modify allografts ex vivo prior to transplantation. In this review, novel therapeutic strategies using recombinant viruses as gene-transfer vehicles and, more recently, the use of gene-modified dendritic cells or regulatory T cells to protect the graft from immune-mediated rejection will be discussed.