Commanding roles of keratocytes in health and disease.

The healthy corneal stroma comprises a 3-dimensional network of keratocytes interconnected by cellular processes divided by gap junctions. The shape of the corneal stromal cells is regulated by the presence of extracellular collagen matrix. Furthermore, if compact collagen are present around keratocytes, they decrease their mitotic activity so that the cells in normal healthy cornea are quiescent with low proliferative activity. However, when extracellular collagen is disrupted such as when inflammatory cells infiltrate the corneal stroma and release proinflammatory cytokines including interleukin 1 and tumor necrosis factor α, keratocytes are released from their network structure and undergo active proliferation. However, culturing keratocytes in the presence of tumor necrosis factor α dose dependently downregulates the presence and function of gap functions. Keratocytes also have phagocytic activities; foreign particles are internalized into these cells. In corneal ulceration, microorganisms invading the stroma secrete collagen-degrading enzymes and signaling molecules such as elastase and lipopolysaccharide that activate corneal keratocytes to secrete stroma-degrading matrix metalloproteinase and various chemokines to attract immune cells to the focus area of corneal stroma. Thus, keratocytes actively participate in collagen degradation of corneal ulceration. The Chinese herbal extract triptolide has been demonstrated significantly and dose dependently to decrease collagen degradation by condition medium-induced corneal fibroblasts. In ocular health, keratocytes respond to signals to and from epithelial cells. In ocular disease, keratocytes become activated cells that respond to various cytokines. Hence, keratocytes play commanding roles in ocular health and disease.