Yin and yang in cytokine regulation of corneal wound healing: roles of TNF-alpha.

During wound healing, corneal tissue has to restore its transparency for proper vision. Various cytokines and growth factors are believed to orchestrate cellular behavior in a healing cornea. This review summarizes the roles of 1 such factor, the proinflammatory cytokine tumor necrosis factor (TNF)-alpha, in the process of wound healing in the cornea. Many studies have shown the anti-transforming growth factor-beta activity of TNF-alpha in cultured cell types. However, it remains unknown whether endogenous TNF-alpha has such an effect in the in vivo healing cornea. Recently, experiments that used TNF-alpha-deficient mice clearly showed that loss of TNF-alpha results in excess inflammation and fibrogenic reaction in response to external stimuli in lung and joint tissue. In the cornea, my group's experiments reveal that the lack of TNF-alpha potentiates pathogenic excess inflammation, fibrogenic response, and neovascularization in an alkali-burned mouse cornea. We uncovered the principal role of the lack of TNF-alpha in invaded macrophages, but not in corneal cells, in the development of this phenomenon by using Smad7 gene transfer, bone marrow transplantation, and cell culture experiments. These findings provide additional information for understanding the role of the cytokine network in corneal wound healing. Further studies are needed to determine if anti-TNF-alpha strategies might be effective in the treatment of ocular surface inflammatory or allergic disorders.