Abstract
Corneal transplantation has not matched the improvements in outcome seen with other clinical transplantation procedures. The therapeutic strategies, which have improved the outcomes of solid vascularised organs are not applicable to corneal transplantation. Corneal transplantation is different with respect to relevant transplantation biology and the clinical context in which it is practiced. New approaches need to be developed which provide regional rather than systemic immunosuppression. The accessibility of the cornea makes it particularly suitable for topical medication and for gene therapy approaches. Engineered antibodies, small enough to pass through the cornea, and directed at key molecules in the allograft response have been developed. Gene therapy had been developed using viral vectors to transfect the corneal endothelium with the genes for immunosuppressive lymphokines. Both approaches show promise.
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References
Williams KA, Lowe MT, Bartlett CM, Kelly L, Coster DJ . The Australian Corneal Graft Registry 2007 Report. Flinders University Press: Adelaide, 2007.
Wolfe RA . Long-term renal allograft survival: a cup half-full and half-empty. Am J Transplant 2004; 4: 1215–1216.
Catry L, Van den Oord J, Foets B, Missotten L . Morphologic and immunophenotypic heterogeneity of corneal dendritic cells. Graefes Arch Clin Ex Ophthalmol 1991; 229: 182–185.
Jager Mj . Corneal Langerhans cells and ocular immunology. Reg Immunol 1992; 4: 186–195.
Williams KA, Ash JK, Coster DJ . Histocompatibility antigen and passenger cell content of normal and diseased human cornea. Transplantation 1985; 39: 265–269.
Williams KA, White MA, Ash JK, Coster DJ . Leukocytes in the graft bed associated with corneal graft failure. Analysis by immunohistology and actuarial graft survival. Ophthalmology 1989; 96: 38–44.
Pepose JS, Gardner KM, Nestor MS, Foos RY, Pettit TH . Detection of HLA class I and II antigens in rejected human corneal allografts. Ophthalmology 1985; 92: 1480–1484.
Bill A . The blood-aqueous barrier. Trans Ophthalmol Soc UK 1986; 105: 149–155.
Streilein JW . Ocular immune privilege: the eye takes a dim but practical view of immunity and inflammation. J Leukoc Biol 2003; 74: 179–185.
Kuffova L, Netukova M, Duncan L, Porter A, Stockinger B, Forrester JV . Cross presentation of antigen on MHC Class II via the draining lymph node after corneal transplantation in mice. J Immunol 2008; 180: 1353–1361.
McMenamin PG, Crew J, Morrison S, Holt PG . Immunomorphologic studies of macrophages and MHC Class II-positive dendritic cells in the iris and ciliary body of the rat, mouse, and human eye. Invest Ophthalmol Vis Sci 1994; 35: 3234–3250.
Banerjee S, Figueiredo FC, Easty DL, Dick AD, Nicholls SM . Development of organized conujunctival leukocyte aggregates after corneal transplantation in rats. Br J Ophthalmol 2003; 87: 1515–1522.
Yamagami S, Dana MR . The critical role of lymph nodes in corneal alloimmunization and graft rejection. Invest Ophthalmol Vis Sci 2001; 42: 1293–1298.
Camelo S, Shanley A, Voon AS, McMenamin PG . The distribution of antigen in lymphoid tissues following its injection into the anterior chamber of the rat eye. J Immunol 2004; 172: 5388–5395.
Liu Y, Hamrah P, Zhang Q, Taylor AW, Dana MR . Draining lymph nodes of corneal transplant hosts exhibit evidence for donor major histocompatibility complex (MHC) class II-positive cells derived from MHC call II-negative grafts. J Exp Med 2002; 195: 259–268.
Choudhuri K, van der Merwe P . Molecular mechanisms involved in T cell receptor triggering. Semin Immunol 2007; 19: 255–261.
Casadei DH, del C Rial M, Opelz G, Golberg JC, Argento JA, Greco G et al. A randomized and prospective study comparing treatment with high-dose intravenous immunoglobulin with monoclonal antibodies for rescue of kidney grafts with steroid-resistant rejection. Transplantation 2001; 71 (1): 53–58.
Cooperative Clinical Trials in Transplantation Research Group. Murine OKT4A immunosuppression in cadaver donor renal allograft recipients: a cooperative clinical trials in transplantation pilot study. Transplantation 1997; 63 (9): 1243–1251.
Salomon B, Bluestone JA . Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation. Annu Rev Immunol 2001; 19: 225–252.
Theil MA, Takano T, Hawksworth N, Coster DJ, Williams KA . Low-dose, short-term treatment with anti-CD4 monoclonal antibody prolongs corneal allograft survival. Transp Proc 2001; 33: 635–636.
Klebe S, Sykes PJ, Coster DJ, Krishnan R, Williams KA . Prolongation of sheep corneal allograft survival by transfer of the gene encoding ovine interleukin 10. Transplantation 2001; 71: 1214–1220.
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Supported by the National Health & Medical Research Council and the Ophthalmic Research Institute of Australia.
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Presented at the Cambridge Ophthalmological Symposium, September 2008
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Coster, D., Jessup, C. & Williams, K. Mechanisms of corneal allograft rejection and regional immunosuppression. Eye 23, 1894–1897 (2009). https://doi.org/10.1038/eye.2009.17
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DOI: https://doi.org/10.1038/eye.2009.17
