Role of apoptosis in eyelid development.

The upper and lower eyelids fuse together during development and then reseparate. The mechanism of reseparation of the eyelids is still unclear, although many reports agree that keratinization has a major role in lid separation. We applied apoptotic detection methods with ultrastructural features to examine the process of lid separation in rats. We confirmed that the eyelids fused on the 18th day of gestation. At this stage, cellular excrescences appeared from the external and conjunctival surfaces overlying the junctional zone, and the junctional zone consisted of epidermal cell clumps with wide intercellular spaces. From the 18th to the 20th day of gestation, many apoptotic cells appeared in the junctional zone and in the cellular excrescences. In these tissues, TUNEL-positive cells and immunohistochemically stained macrophages were found at this stage. We conclude that apoptosis may eliminate external and conjunctival cellular excrescences to make both surfaces smooth and continuous across the junctional zone. Apoptosis may also play a major role in providing space for proliferation of newly organized epidermal cells without wide intercellular spaces. Subsequent keratinization extends onto epidermal and conjunctival sides of the junctional zone until separation of the lids is complete.