Second injury in the cornea - The role of inflammatory cytokines in corneal damage and repair

Purpose. Inflammation of the cornea often leads to corneal tissue destruction, e.g., corneal ulcer or perforation; however, little is known about the association between corneal inflammation and tissue destruction. Methods. In our most recent experiments, interleukin (IL)-1 and IL-6 production was induced in the early stages after alkali injury to the cornea. Upregulation of inflammatory cytokines during alkali injury is thought to play an important role in inflammatory cell infiltration and tissue destruction, especially as it can induce matrix metalloproteinase (MMP) production. In another experiment, we showed that topical application of an MMP inhibitor to alkali-injured mouse corneas reduces the expression of inflammatory cytokines and the severity of the injury. Results. Based on our findings and those of others, we describe the role of cytokines in corneal inflammation and tissue destruction. We also propose the hypothesis that a vicious cycle may be initiated after the first injury to the cornea, with "second injury to the cornea" occurring because of the action of inflammatory cytokines. Conclusion. We believe that the concept of second injury is important in the successful management of inflammatory corneal diseases.