Treatment strategy for rejection-free corneal transplantation--transition from full-thickness corneal transplantation to corneal endothelium transplantation

The avoidance of allograft rejection is the most critical factor for favorable surgical outcome after corneal transplantation. We report experimental data including distribution of white blood cells in human corneas for rejection-free corneal transplantation. We focused on leukocyte trafficking based on the immunological mechanism leading to allograft rejection in a mouse full-thickness corneal transplantation model. We identified two chemokine-receptors, CCR1 and CCR7 which are functionally relevant to the occurrence of allograft rejection. These chemokine receptors can be new targets for the suppression of allograft rejection after full-thickness corneal transplantation. In the human corneas, bone marrow-derived dendritic cells and monocyte-lineage cells reside constitutively in the normal epithelium and stroma, and may be associated with direct recognition of allo-antigen after corneal transplantation. We established a mouse model in which cultured allocorneal endothelium was transplanted onto a bullous keratopathy recipient cornea. During the follow-up period, the transplanted cultured allo-corneal endothelium did not show any sign of allograft rejection. Our findings demonstrated that a rejection-free mechanism is due not to suppression of immunity or to lack of response, but to failure to recognize the existence of resistance. Realization of the clinical application of cultured allo-corneal endothelium transplantation may be a shortcut to ideal rejection-free corneal transplantation.