Immunology of Corneal Allografts: Insights from Animal Models.

Abstract

Corneal transplantation stands alone as the most common and successful form of solid organ transplantation. Even though HLA matching and systemic antirejection drugs are not routinely used, 90% of the first time corneal allografts will succeed. By contrast, all other major categories of organ transplantation require HLA matching and the use of systemically administered immunosuppressive drugs. This remarkable success of corneal transplants under these conditions is an example of "immune privilege" and is the primary reason for the extraordinary success of corneal transplantation. A number of dogmas have emerged over the past century to explain immune privilege and the immunobiology of corneal transplantation. Many of these dogmas have been based largely on inferences from clinical observations on keratoplasty patients. The past 30 years have witnessed a wealth of rodent studies on corneal transplantation that have tested hypotheses and dogmas that originated from clinical observations on penetrating keratoplasty patients. Rodent models allow the application of highly sophisticated genetic and immunological tools for testing these hypotheses in a controlled environment and with experiments designed prospectively. These studies have validated some of the widely held assumptions based on clinical observations and in other cases, previous dogmas have been replaced with new insights that could only come from prospective studies performed under highly controlled conditions. This review highlights some of the key dogmas and these widely held assumptions that have been scrutinized through the use of rodent models of penetrating keratoplasty. This review also makes note of new immunological principles of corneal immunology that have emerged from rodent studies on corneal transplantation that most likely would not have been revealed in studies on corneal transplantation patients.