Animal models of high-risk corneal transplantation: A comprehensive review

Abstract

Over the past century, corneal transplantation has become the most commonly performed allogeneic solid tissue transplantation. Although more than 80% of the corneal transplantations have favorable outcomes, immune-mediated rejection continues to be the major cause of failure in well over 50% of graft recipients that have inflamed and vascularized host beds. Over the past two decades, the progress in our understanding of the immunological pathways that mediate graft rejection has aided in the development of novel therapeutic strategies. In order to successfully test the efficacy of these interventions, it is essential to model the immunological processes occurring as a consequence of corneal transplantation. Herein, we have comprehensively reviewed the established animal models used for replicating the immunopathological processes causing graft rejection in high-risk corneal transplantation settings. We have also discussed the practical and technical differences, as well as biological and immunological variations in different animal models.

Keywords: ACAID; Allergic conjunctivitis; High risk corneal transplantation; Penetrating keratoplasty; neovascularization.

Figure 1:. Schematic illustration of major existing models of inducing high-risk recipient bed in corneal transplantation.

The recipient graft bed is divided into five segments, each demonstrating a different procedure for generation of high-risk graft recipient bed (order clockwise): (1) Induction of neovascularization (NV) in the recipient bed by sutures (NV model); (2) Bringing iris vessels in physical contact with the cornea through anterior synechiae (Anterior synechiae model); (3) Abrogation of ACAID via splenectomy or depletion of NKT and γδ cells (ACAID model); (4) Pre-sensitization of recipient graft bed via application of allergens (Allergic model); and (5) Langerhans cell (LC) penetration into the graft bed by using the latex beads technique (LC model).