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Purpose: Here we investigate the role of donor endothelium on allograft rejection in a lamellar keratoplasty (LK) model using grafts with or without donor endothelium. Methods: Corneal buttons of donor C57BL/6 mice (2.0 mm) were transplanted to lamellar recipient beds (1.5 mm) in BALB/c mice. Two variations of the LK procedure were performed: (1) standard LK (SLK) (n = 13) without donor endothelium and (2) modified LK (MLK) (n = 14) with retained donor endothelium. The graft status was assessed by slit lamp biomicroscopy and scored for stromal opacity, corneal edema, neovascularization, and anterior chamber reaction up to 46 days post-transplantation. Corneas were also observed histologically. Results: The presence of a grafted corneal endothelium promoted graft rejection; 92.9% (13/14) of grafts were rejected in MLK after an average of 8.3 days, while 69.2% (9/13) of grafts were rejected in SLK on average 10.8 days after transplantation. The former's stromal opacity was significantly greater at all time points after day 14 except for day 21 (p = 0.77) and day 32 (p = 0.25). Corneal edema was significantly greater in the former at all time points after day 10 except for day 21 (p = 0.16). Neovascularization was significantly greater in the former at all time points after day 10 except for day 25 (p = 0.22). Conclusion: Variations of this model of LK may be useful for studies of immunological mechanisms in corneal transplantation. The donor corneal endothelium may serve as a target of the immune response which promotes inflammation, neovascularization, and graft rejection. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]