Oral immunisation as a strategy for enhancing corneal allograft survival

Aims--To determine optimal conditions for enhancing corneal allograft survival through oral administration of donor specific corneal cells. Methods--A mouse model of penetrating keratoplasty was used to evaluate the efficacy and optimal conditions for preventing immunological rejection of corneal allografts. C3H corneal grafts were transplanted orthotopically to CB6F1 recipients and represented mismatches at the entire major histocompatibility complex (MHC) and multiple minor histocompatibility loci. Tissue cultured C3H corneal epithelial and endothelial cells were administered orally to CB6F1 mice before or shortly after the application of orthotopic C3H corneal allografts. Cultured C3H corneal cells were conjugated with the non-toxic B subunit of cholera toxin as a means of preferentially inducing oral tolerance. Results--Ten oral doses of donor cells administered before keratoplasty reduced the incidence of corneal graft rejection from 100% in untreated hosts to 54% in orally tolerised mice. Conjugation of cholera toxin to corneal cells significantly enhanced the efficacy of oral tolerance such that only 9% of the mice fed 10 doses of cholera toxin conjugated cells rejected their corneal grafts. Even a single oral inoculation of corneal cells conjugated to cholera toxin was able to reduce corneal graft rejection by 36%. Conclusions--Oral administration of donor specific cells greatly enhances corneal graft survival. Use of cholera toxin adjuvant markedly enhances the efficacy of oral tolerance such that even a single oral dose of donor cells significantly reduces the incidence of rejection. The results support the clinical feasibility of this novel strategy for preventing immunological rejection of corneal transplants.