Histopathologic features of rejecting orthotopic corneal xenografts

Discordant xenogeneic Hartley guinea pig corneal buttons were transplanted orthotopically to either naive or pre-immune Lewis rats. Recipients were sacrificed serially and grafts were immediately frozen and subsequently examined using standard immunohistologic techniques. Corneal xenografts remained clear in naive recipients for 7 days, at which point they rapidly became opaque and edematous. In pre-immunized recipients, corneal xenografts were rejected much more quickly, becoming opaque and edematous by day 3 post-transplantation. Histologic examination of grafts revealed severe stromal edema and diffuse inflammatory cell infiltrates composed of mononuclear cells and neutrophils. Infiltrates were present as early as day 2 in xenografts from both presensitized and naive recipients. The infiltrates were densest in the posterior half of the grafts with fewer cells penetrating into the epithelium. Immunoperoxidase staining confirmed the presence of OX-19+ T cells as well as a substantial infiltrate of OX-42+ neutrophils/macrophages. Additionally, IgG was deposited throughout the grafts in a diffuse manner. Deposition of IgG was accelerated in presensitized recipients, with intense staining of the entire graft detected by day 2. Examination of the rejected grafts suggests that rejection occurs via mechanisms similar to those seen in corneal allografts. This, in turn, implies corneal xenografts may be amenable to standard immunosuppressive regimens.