The production of kynurenines, in particular 3HK and 3HAA, may be one mechanism (in addition to tryptophan depletion) by which IDO prolongs graft survival. These molecules have potential as specific agents for preventing allograft rejection in patients at high rejection risk.

The cornea is an immune privileged tissue. Since arginase has been found to modulate T-cell function by depleting arginine, we investigated the expression of arginase in the cornea and its possible role in immune privilege using a murine transplant model. We found that both the endothelium and epithelium of murine corneas express functional arginase I, capable of down-regulating T-cell proliferation in an in vitro culture system. The administration of the specific arginase inhibitor N-hydroxy-nor-l-Arg to recipient mice resulted in an accelerated rejection of allogeneic C57BL/6 (B6) corneal grafts. In contrast, in vivo blockade of arginase activity had no effect in altering the course of rejection of primary skin grafts that express little, if any, arginase. In addition, the inhibition of arginase did not alter systemic T-cell proliferation. These data show that arginase is functional in the cornea and contributes to the immune privilege of the eye, and that modulation of arginase contributes to graft survival.

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Limbal stem cell damage after chemical injury, autoimmune disorders or iatrogenic trauma leads to corneal conjunctivalisation with new vessel formation, epithelium instability and visual loss. Limbal stem cell transplantation includes reconstructive surgical procedures to restore a corneal epithelium. The recognised options are: conjunctival limbal autograft, in which stem cells are taken from the patient’s healthy eye; conjunctival limbal allograft, in which stem cells are taken from a living, related or dead donor and the keratolimbal allograft. Each of these procedures has some drawbacks; in particular, the conjunctival limbal autograft needs a relatively healthy fellow eye and needs a relatively large amount of donor tissue from the healthy eye (about one-third of the healthy limbal stem cell tissue) with potential risks to the donor eye. In the case of keratolimbal allograft transplants, the recipient needs an immunosuppressive treatment to reduce the risk of rejection with the associate possible side effects. More modern treatment options are reviewed. Cultivated oral mucosa epithelial transplantation success rate can vary between 50% and 70% at 3–4 years of follow-up. Simple limbal epithelial transplantation results show a success rate from 75.2% to 83.8% after 1 year of follow-up. Inclusion criteria for autologous cultivated limbal epithelial transplantation as approved by the National Institute of Health and Care Excellence are also shown in this paper. On the basis of these more contemporary treatment options, a stepladder approach to evaluate which procedure is most appropriate and personalised to the patient’s conditions is proposed.