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178 Khodadoust and Silverstein Investigative Ophthalmology April 1969 infiltrate, in front of which lies apparently normal donor epithelium, and behind which is found a thin layer of recipient epithelium sliding in to heal the defect. Most significant in the present discussion is the fact that whenever this epithelial rejection commences, even 6 months after transplantation, it always starts precisely at the margin of the graft, indicating quite clearly that there has been no substitution of host for donor epithelial cells across the graft border. The characteristic migrating epithelial line described is considered to be a specific allograft rejection reaction to donor epithelium based upon the following observations : 1. It occurs only on allografts when the donor epithelium is intact; on no occasion was a similar phenomenon seen involving autograft epithelium, or on the surface of allografts when the donor epithelium was removed prior to transplantation and permitted to be replaced by recipient epithelium. 2. It is not a nonspecific response to the rejection of underlying stroma, since it has been observed to precede, to follow, or to progress in concert with the rejection of stroma. Furthermore, rejection of the pure stromal allograft covered by host epithelium is unaccompanied by a similar epithelial defect. Finally, preliminary work with pure epithelial allografts ls indicates that donor epithelial rejection may take place over the surface of the host's own stroma and endothelium. 3. The starting point, extension, and direction of migration of the epithelial rejection line are invariably related closely to the extent and distribution of corneal vascularization near the graft margin, and the moving epithelial defect is never seen to extend beyond the boundary of the donor graft onto host cornea. 4. In the mildly vascularized lamellar graft in which rejection does not occur spontaneously, epithelial rejection may be induced by orthotopic skin transplantation only from the same donor which provided the corneal graft. 5. In the heavily vascularized lamellar allograft, the minimal time of epithelial rejection (14 days) is the same as that observed by Billingham and Boswell 19 in their study of the rejection of corneal grafts transplanted ectopically onto a vascularized bed formed on the skin. Moreover, the rejection of epithelium on the corneal graft has been found to be accompanied by sensitization of the host, as evidenced by second-set rejection of a skin graft from the same donor. We wish to express our appreciation for the competent technical assistance of Mahmood Farazdaghi. REFERENCES 1. Basu, P. K., Miller, I., and Ormsby, H. L.: Sex chromatin as a biologic cell marker in the study of the fate of corneal transplants, Am. J. Ophth. 49: 513, 1960. 2. Hanna, C, and Irwin, E. S.: Fate of cells in the corneal graft, Arch. Ophth. 63: 810, 1962. 3. Polack, F. M., Smelser, G. K., and Rose, J.: Long-term survival of isotopically labeled stromal and endothelial cells in corneal homografts, Am. J. Ophth. 57: 67, 1964. 4. Chi, H. H., Teng, C. C, and Katzin, H. M.: The fate of endothelial cells in corneal homografts, Am. J. Ophth. 59: 186, 1965. 5. Khodadoust, A. A.: Lamellar corneal transplantation in the rabbit, Am. J. Ophth. 66: 1111, 1968. 6. Khodadoust, A. A.: Penetrating corneal transplantation in the rabbit, Am. J. Ophth. 66: 899, 1968. 7. Khodadoust, A. A., Silverstein, A. M., and Maumenee, A. E.: Allograft rejection of experimental lamellar corneal transplants. In preparation. 8. Khodadoust, A. A., Silverstein, A. M., and Maumenee, A. E.: Allograft rejection of experimental penetrating corneal transplants. In preparation. 9. Polack, F. M., and Smelser, G. K.: The persistence of isotopically labeled cells in corneal grafts, Proc. Soc. Exper. Biol. & Med. 110: 60, 1962. 10. Hanna, C, and O'Brien, J. E.: Cell production and migration in the epithelial layer of the cornea, Arch. Ophth. 64: 536, 1960. 11. Bonnefon, G., and Lacoste, A.: Recherches
Volume 8 Number 2 Epithelium survival and rejection 179 histologiques sur la grefFe corneenne autoplastique, Arch. f. Ophth. 33: 206; 267; 326, 1913. 12. Offret, C: The histopathology of the corneal graft, in Rycroft, B. W., editor: Corneal grafts, London, 1955, Butterworth & Co., p. 36. 13. Maumenee, A. E., and Kornblueth, W.: In Symposium on corneal transplantation. IV. Physiopathology, Trans. Am. Acad. Ophth. 50: 331, 1948. 14. Dohlman, C. H.: On the fate of the corneal graft, Acta ophth. 35: 286, 1957. 15. Kornblueth, W., and Nelken, E.: A study on donor-recipient sensitization in experimental homologous partial lamellar corneal grafts, Am. J. Ophth. 45:843, 1958. 16. Mizukawa, T., Otori, T., Hara, J., Fujita, N., and Okuhara, S.: The movement of the epithelial cells after lamellar homokeratoplasty studied by autoradiography, Jap. J. Ophth. 7: 196, 1963. 17. de Ocampo, C, and Sunga, R. N.: Studies on the epithelization of corneal grafts with methylene blue, Am. J. Ophth. 56: 801, 1963. 18. Khodadoust, A. A., and Silverstein, A. M.: Transplantation and rejection of individual cell layers of the cornea, INVEST. OPHTH. 8: 180, 1969. 19. Billingham, R. E., and Boswell, T.: Studies on the problem of corneal homografts, Proc. Roy. Soc, London, Ser. B 141: 392, 1953.
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