Abstract
In addressing the worldwide shortage of human donor cornea for transplantation, animal cornea may be a substitute if mechanisms of xenogeneic (cross-species) rejection can be identified and controlled. Xenotrans-plantation of solid organs is followed by hyperacute rejection within minutes due to humoral graft rejection. In an experimental model corneal xenografts in rats survived for 2-3 days, depending on the phylogenetic disparity of the donor animal. Endothelial injury was the specific cause of graft failure, probably mediated by humoral rejection mechanisms. A later cell-mediated rejection response was seen. The potent humoral response is the most important feature differentiating xenograft from allograft rejection.
Similar content being viewed by others
Article PDF
References
Reemtsma K, McCracken BH, Schlegel JV, Pearl M . Heterotransplantation of the kidney: two clinical experiences. Science 1964;143:700–2.
Hitchcock CR, Kiser JC, Telander RL, Seljeskog EL . Baboon renal grafts. JAMA 1964;189:158–61.
Starzl TE, Marchioro TL, Peters GN, et al Renal heterotransplantation from baboon to man: experience with 6 cases. Transplantation 1964;2:752–76.
Bailey LL, Nehlsen-Cannarella SL, Concepcion W, Jolley WB . Baboon-to-human cardiac xenotransplantation in a neonate. JAMA 1985;254:3321–9.
Auchincloss H . Xenogeneic transplantation. Transplantation 1988;46:1–20.
Starzl TE, Fung J, Tzakis A, et al Baboon-to-human liver transplantation. Lancet 1993;341:65–71.
Perper RJ, Najarian JS . Experimental renal heterotransplantation. I. In widely divergent species. Transplantation 1966;4:377–88.
Giles GR, Boehmig HJ, Lilly J, et al Mechanism and modification of rejection of heterografts between divergent species. Transplant Proc 1970;2:522–37.
Rosenberg JC, Broersma RJ, Bullemer G, Mammen EF, Lenaghan R, Rosenberg BE Relationship of platelets, blood coagulation and fibrinolysis to hyperacute rejection of renal xenografts. Transplantation 1969;8:152–61.
Cattell V, Jamieson SW . Hyperacute rejection of guinea-pig to rat cardiac xenografts. I. Morphology. J Pathol 1975;115:183–9.
Rose AG, Cooper DKC, Human PA, Reichenspurner H, Reichart B . Histopathology of hyperacute rejection of the heart: experimental and clinical observations in allografts and xenografts. J Heart Lung Transplant 1991;10:223–34.
Galili U, Rachmilewitz EA, Peleg A, Flechner I . A unique natural human IgG antibody with anti-alpha-galactosyl specificity. J Exp Med 1984;160:1519–27.
Galili U, Clark MR, Shohet SB, Buehler J, Macher BA . Evolutionary relationship between the natural anti-gal antibody and the Galal-3Gal epitope in primates. Proc Natl Acad Sci USA 1987;84:1369–73.
Sandrin MS, Vaughan HA, Dabkowski PL, McKenzie IFC . Anti-pig IgM antibodies in human serum react predominantly with Gal(al-3)Gal epitopes. Proc Natl Acad Sci USA 1993;90:11391–5.
Platt JL, Lindman BJ, Chen H, Spitalnik SL, Bach FH . Endothelial cell antigens recognised by xenoreactive human natural antibodies. Transplantation 1990;50:817–22.
Miyagawa S, Hirose H, Shirakura R, et al The mechanism of discordant xenograft rejection. Transplantation 1988;46:825–30.
Vercellotti GM, Platt JL, Bach FH, Dalmasso AP . Enhanced neutrophil adhesion to xenogeneic endothelium via iC3b. J Immunol 1991;146:730–4.
Platt JL, Lindman BJ, Geller RL, et al The role of natural antibodies in the activation of xenogeneic endothelial cells. Transplantation 1991;52:1037–43.
Johnston PS, Wang M-W, Lim SML, et al Discordant xenograft rejection in an antibody-free model. Transplantation 1992;54:573–6.
Gambiez L, Salame E, Chereau C, et al The role of natural IgM in the hyperacute rejection of discordant heart xenografts. Transplantation 1992;54:577–83.
Calne RY . Observations on renal homotransplantation. Br J Surg 1961;48:384–91.
Kissam RS . Ceratoplastice in man. NY J Med Collat Sci 1844;2:281–2.
Von Hippel A . Eine neue Methode der Hornhauttransplantation. Graefes Arch Clin Exp Ophthalmol 1888;34:108–30.
Harrison RG . Heteroplastic grafting in embryology. Harvey Lect 1935;29:116–57.
Babel J, Bourquin JB . Experimental research with corneal heterografts. Br J Ophthalmol 1952;36:529–36.
Choyce DP . Successful transplantation of human and cat corneal tissue into rabbit corneae. Br J Ophthalmol 1952;36:537–42.
Paul SD . Hetero-corneal transplantation in experimental animals. Ophthalmologica 1964;147:334–42.
Silverstein AM, Rossman AM, de Leon AS . Survival of donor epithelium in experimental corneal xenografts. Am J Ophthalmol 1970;69:448–53.
Lee DS, Basu PK . A comparative study of the corneal graft reaction in allo- and xenogeneic models. Can J Ophthalmol 1973;8:444–50.
Doughman DJ, Miller GE, Mindrup EA, Harris JE . The fate of experimental organ-cultured corneal xenografts. Transplantation 1976;22:132–7.
Kuwabara Y . Studies on heterotransplantation of corneas. Am J Ophthalmol 1962;53:911–7.
Soomsawasdi B, Romayanonda N, Bhadrakom S . Hetero-keratoplasty using gibbon donor corneae. Trans Asia-Pacific Acad Ophthalmol 1964;2:251–61.
Ross JR, Howell DN, Sanfilippo FP . Characteristics of corneal xenograft rejection in a discordant species combination. Invest Ophthalmol Vis Sci 1993;34:2469–76.
Larkin DFP, Takano T, Standfield SD, Williams KA . Experimental orthotopic corneal xenotransplantation in the rat: mechanisms of graft rejection. Transplantation 1995 (in press).
Williams KA, Coster DJ . Penetrating corneal transplantation in the inbred rat: a new model. Invest Ophthalmol Vis Sci 1985;26:23–30.
Reding R, Davies H, White D, et al Effect of plasma exchange on guinea pig-to-rat heart xenografts. Transplant Proc 1989;21:534–6.
Leventhal JR, Flores HC, Gruber SA, et al Evidence that 15-deoxyspergualin inhibits natural antibody production but fails to prevent hyperacute rejection in a discordant xenograft model. Transplantation 1992;54:26–31.
Terasaki PI, Esail ML, Cannon JA, Longmire WP . Destruction of lymphocytes in vitro by normal serum from common laboratory animals. J Immunol 1961;87:383–95.
Geller RL, Bach FH, Turman MA, Casali P, Platt JL . Evidence that polyreactive antibodies are deposited in rejected discordant xenografts. Transplantation 1993;55:168–72.
Turman MA, Casali P, Notkins AL, Bach FH, Platt JL . Polyreactivity and antigen specificity of human xenoreactive antibodies. Transplantation 1991;52:710–7.
Nakamura M, Burastero SE, Notkins AL, Casali P . Human monoclonal rheumatoid factor-like antibodies from CD5 (Leu-1)+ ? cells are polyreactive. J Immunol 1988;140:4180–6.
McClellan BH, Whitney CR, Newman LP, Allansmith MR . Immunoglobulins in tears. Am J Ophthalmol 1973;76:89–101.
Cole DF . Ocular fluids. In: Davson H, editor. The Eye. Vol. la. 3rd ed. London: Academic Press, 1969: 269–390.
Raviola G . Effects of paracentesis on the blood-aqueous barrier : an electron microscope study on Macaca mulatta using horseradish peroxidase as a tracer. Invest Ophthalmol 1974;13:828–58.
Chandler JW, Leder R, Kaufman HE, Caldwell JR . Quantitative determinations of complement components and immunoglobulins in tears and aqueous humor. Invest Ophthalmol 1974;13:151–3.
Mondino BJ, Ratajczak HV, Goldberg DB, Schanzlin DJ, Brown SI . Alternate and classical pathway components of complement in the normal cornea. Arch Ophthalmol 1980;98:346–9.
Bora NS, Gobleman CL, Atkinson JP, Pepose JS, Kaplan HJ . Differential expression of the complement regulatory proteins in the human eye. Invest Ophthalmol Vis Sci 1993;34:3579–84.
Manning DD, Reed ND, Shaffer CF . Maintenance of skin xenografts of widely divergent phylogenetic origin on congenitally athymic (nude) mice. J Exp Med 1973;138:488–94.
Martinez OM, Ascher NL, Ferrell L, et al. Evidence for a non-classical pathway of graft rejection involving interleukin-5 and eosinophils. Transplantation 1993:55:909–18.
Hsu GK, Hsu SH, Whitney RA, Hansen CT . Immunopathology of schistosomiasis in athymic mice. Nature 1976;262:397–9.
Campbell HD, Tucker WQJ, Hort Y, et al. Molecular cloning, nucleotide sequence, and expression of the gene encoding human eosinophil differentiation factor (interleukin 5). Proc Natl Acad Sci USA 1987;84:6629–33.
Yamaguchi Y, Suda T, Suda J, et al. Purified interleukin 5 supports the terminal differentiation and proliferation of murine eosinophilic precursors. J Exp Med 1988;167:43–56.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Larkin, D., Williams, K. The host response in experimental corneal xenotransplantation. Eye 9, 254–260 (1995). https://doi.org/10.1038/eye.1995.49
Issue Date:
DOI: https://doi.org/10.1038/eye.1995.49