Comparative immunological study of penetrating and anterior lamellar keratoplasty in a murine model

Abstract

In lamellar keratoplasty, the diseased part of a cornea is replaced while the healthy tissue remains lamellar keratoplasty has the advantage of better graft survival compared to penetrating keratoplasty (PK). We compared the immunological responses to PK and anterior lamellar keratoplasty (ALK) in a murine model. PK or ALK was performed using C57BL/6 donor grafts and BALB/c recipients, and graft opacity was assessed to evaluate graft rejection up to 8 weeks. We evaluated the immunological responses in both groups, which were not clinically considered as graft failure on postoperative day 21. PK mice showed reduced clinical graft survival compared to ALK mice. The mRNA expression of inflammatory mediators, such as IL-1β, IFN-γ, and granzyme B, in grafted corneas of PK mice, was significantly increased compared to the levels in ALK mice at postoperative day 21. PK led to a higher delayed-type hypersensitivity response and IFN-γ secretion in an in vitro T cell assay from draining lymph nodes (LNs), as compared to ALK. Furthermore, PK showed increased angiogenesis and lymphangiogenesis in grafted corneas compared to ALK and led to greater infiltration of CD3⁺ T cells into grafted corneas and increased frequencies of mature antigen presenting cells (APC; MHC-II^highCD11c + cells) and IL-12 + dendritic cells (DCs) in the draining LNs of transplanted mice. In conclusion, PK results in increased graft rejection compared to ALK through relatively increased neovascularization and lymphangiogenesis, which can induce infiltration of pathologic T cells and mature APC migration into grafted corneas and draining LNs.