Expression of cyclin-dependent kinase inhibitors during corneal wound repair.

During corneal epithelial wound repair, cells migrating to cover the wound area exhibit a drastic reduction in proliferative activity. In contrast, cells distal to the original wound exhibit a greatly enhanced level of proliferative activity. At least 90% of the basal cells in limbal and peripheral corneal epithelia synchronously progress through the cell cycle. The question addressed in this article is whether cyclin-dependent kinase inhibitors play a role in the alterations in proliferative activity seen during corneal wound repair. These inhibitors specifically block cells in the G1-phase of the cell cycle. Two families of cyclin-dependent kinase inhibitors have been identified. The CIP/KIP family includes p21, p27, and p57, while the INK4 family consists of p16. p15. p18. and pI9. At least five of these inhibitors are present in the corneal epithelium. The expression of two of these, p15 and p27. is dramatically altered during wound repair, suggesting that they may be involved in the changes in cell proliferation observed during corneal wound healing.