OCULAR RESURFACING AND ALLOEPITHELIAL REJECTION IN A MURINE KERATOEPITHELIOPLASTY MODEL

Purpose. To determine definitively the epithelial origin of corneal re surfacing and to elucidate the immunologic mechanisms of epithelial re jection in a murine keratoepithelioplasty (KEP) model. Methods. After corneal epithelial removal and peritomy, donor corneal lenticules were grafted around the limbus (KEP procedure). The process of corneal ree pithelialization 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, C5 7BL/6, BALB.K, DBA/2, and B10.D2 allogeneic corneal lenticules were gr afted to BALB/c mice, and A.SW and A.TL allogeneic corneal lenticules were grafted to A.TH mice. Alloepithelial rejection was evaluated On t he basis of clinical findings and histologic changes in grafted cornea s. Results, All KEP grafts were reepithelialized entirely at 3 days af ter surgery. The renewed epithelium proved to be derived from the lent icules 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 corn ea. Then followed four characteristic phases of inflammatory epithelia l response: initial phase, acute phase, chronic phase, and rejected ph ase. Histologic examination confirmed the progress and severity of inf lammatory response. The mean onset times of initial phase in assorted grafts with mismatched histocompatibility antigens were: 7.9 +/- 1.8 d ays for both major and minor disparity grafts, 9.5 +/- 3.8 days for ma jor disparity grafts, 18.2 +/- 5.5 days for major histocompatibility c lass I disparity grafts, 25.6 +/- 7.2 days for major histocompatibilit y class II disparity grafts, and 9.2 +/- 2.2 days for multiple minor d isparity grafts. Conclusions. In donor corneal lenticule grafting to h ost eyes with corneal epithelium removed and conjunctival peritomy, th e ocular surface was reepithelialized by lenticule-derived epithelium. Alloepithelial rejection in this model displayed characteristic manif estations and well-defined processes, enabling easy and precise evalua tion of onset and intensity of graft rejection. Both major and minor h istocompatibility antigens are related to corneal epithelial rejection .