Mechanisms of corneal damage associated with ocular surface inflammation

The cornea is a transparent tissue composed of epithelial cells, stromal keratocytes embedded in collagen fibers, and endothelial cells. Inflammation at the ocular surface can damage the cornea, which may become swollen or scarred, resulting in a loss of its clarity. In particular, the barrier function of the corneal epithelium can be disrupted by ocular surface inflammation, leading to adverse effects on the structure and function of the corneal stroma. Various cytokines and chemokines contribute to the inflammatory response at the ocular surface, with the proinflammatory cytokines tumor necrosis factor–α (TNF-α) and interleukin-1β (IL-1β) in particular playing key roles in this response. Intercellular junctions such as adherens junctions, tight junctions, and gap junctions that form between adjacent corneal epithelial cells or stromal keratocytes are essential for the maintenance of corneal homeostasis. To provide insight into the mechanisms of corneal damage induced by inflammation, we have examined the effects of TNF-α and IL-1β on tight junctions and adherens junctions in cultured monolayers of human corneal epithelial cells as well as on gap junctions in cultured stromal keratocytes. We here review the results of our recent studies and their implications for the development of new approaches to ameliorate or prevent corneal disorders associated with ocular surface inflammation.

tumor necrosis factor–α (TNF-α)

interleukin-1β (IL-1β)

tight junction

adherens junction

gap junction