Proliferation and apoptosis in the epithelium of the developing human cornea and conjunctiva

To determine the distribution of proliferating and apoptotic cells in the h uman cornea during prenatal and early postnatal development, we examined se ctions of the bulbar conjunctiva, the limbus as well as the central and per ipheral cornea between 11 weeks of gestation and 6 months after birth. The objective was to localize dividing cells by proliferating cell nuclear anti gen-like immunoreactivity (PCNA-LI) and apoptotic cells by terminal transfe rase-mediated nick-end labeling (TUNEL). Before the 17th gestational week, PCNA-LI was absent in all 4 regions examined, indicating negligible cell pr oliferation during early development. After 20 weeks, strong PCNA-labeling was observed in all regions examined suggestive of high proliferative activ ity not only in the limbus and the bulbar conjunctiva, but also in the cent ral and peripheral cornea. This rise in proliferative activity was followed by a steady decline: after 28 weeks, anti-PCNA staining gradually disappea red in the central and peripheral cornea, so that, at 6 months after birth, it was confined to the limbus and the bulbar conjunctiva, resembling the p icture described for the adult cornea. TUNEL-positive cells were Virtually absent in all 4 regions examined before the 38th gestational week. Apoptoti c cells only started to appear at 38 weeks; at this stage, they were confin ed to the bulbar conjunctival epithelium. At 6 months after birth, TUNEL-po sitive cells were observed in the bulbar conjunctival epithelium and the en tire cornea; the limbus, however remained devoid of apoptotic cells through out the entire prenatal and early postnatal period. The present study for t he first time localizes proliferating and apoptotic cells in the epithelium of the developing human cornea. Three stages of development can be disting uished: Minimal proliferation (until 17th week), vigorous proliferation ove r the entire cornea including the limbus and the bulbar conjunctiva (until 28th week) and gradual decrease in proliferative activity (after 28th week) accompanied by the appearance of apoptotic cells. (C) 2001 Elsevier Scienc e Inc. All rights reserved.