Proteolytic mechanisms in corneal ulceration and repair

Corneal stromal ulceration is a devastating disorder that can cause blindness. Stromal ulceration was once thought to be a physical dissolution process, which even now is described as "melting." However, a major paradigm change occurred about 25 years ago with the demonstration of extracellular matrix-degrading activity associated with tissues isolated from ulcerating corneas. Recent studies have identified the enzymes involved as specific members of the matrix metalloproteinase (MMP) family. These studies have further provided evidence that MMPs participate at all stages of the ulcerative process, from formation of the initiating epithelial defect to ulcer resolution and repair. Roles for MMPs in these processes are discussed in this review. Studies on corneal ulceration provide basic information about failure to heal, which is useful for understanding mechanisms common to other organ systems besides the cornea.