Ocular resurfacing and alloepithelial rejection in a murine keratoepithelioplasty model

To determine definitively the epithelial origin of corneal resurfacing and to elucidate the immunologic mechanisms of epithelial rejection in a murine keratoepithelioplasty (KEP) model.

After corneal epithelial removal and peritomy, donor corneal lenticules were grafted around the limbus (KEP procedure). The process of corneal reepithelialization was observed with 0.25% methylene blue staining. The origin of the renewed epithelium was determined by immunofluorescence. Syngeneic corneal lenticules were grafted to BALB/c mice. C3H/He, C57BL/6, BALB.K, DBA/2, and B10.D2 allogeneic corneal lenticules were grafted to BALB/c mice, and A.SW and A.TL allogeneic corneal lenticules were grafted to A.TH mice. Alloepithelial rejection was evaluated on the basis of clinical findings and histologic changes in grafted corneas.

All KEP grafts were reepithelialized entirely at 3 days after surgery. The renewed epithelium proved to be derived from the lenticules in BALB/c eyes receiving C3H/He lenticules. In syngeneic grafts 5 days after KEP, the cornea recovered clarity and smoothness, which persisted to the end of the study. After complete reepithelialization, all allogeneic grafts also experienced a short duration of clear cornea. Then followed four characteristic phases of inflammatory epithelial response: initial phase, acute phase, chronic phase, and rejected phase. Histologic examination confirmed the progress and severity of inflammatory response. The mean onset times of initial phase in assorted grafts with mismatched histocompatibility antigens were: 7.9 +/- 1.8 days for both major and minor disparity grafts, 9.5 +/- 3.8 days for major disparity grafts, 18.2 +/- 5.5 days for major histocompatibility class I disparity grafts, 25.6 +/- 7.2 days for major histocompatibility class II disparity grafts, and 9.2 +/- 2.2 days for multiple minor disparity grafts.

In donor corneal lenticule grafting to host eyes with corneal epithelium removed and conjunctival peritomy, the ocular surface was reepithelialized by lenticule-derived epithelium. Alloepithelial rejection in this model displayed characteristic manifestations and well-defined processes, enabling easy and precise evaluation of onset and intensity of graft rejection. Both major and minor histocompatibility antigens are related to corneal epithelial rejection.