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Proliferation and apoptosis in the epithelium of the developing human cornea and conjunctiva
1Department of Anatomy, The Chinese University of Hong Kong, Shatin, New Territories. b175750@mailserv.cuhk.edu.hk
Insights
Cell proliferation in the developing human cornea is minimal early on, peaks between 20-28 weeks, and then declines. Apoptotic cells appear later, primarily in the cornea and conjunctiva, but not the limbus.
Area of Science:
- Ophthalmology
- Developmental Biology
- Cell Biology
Background:
- Understanding human cornea development is crucial for regenerative medicine and treating ocular diseases.
- Cell proliferation and apoptosis are key processes regulating tissue development and homeostasis.
Purpose of the Study:
- To map the spatiotemporal distribution of proliferating and apoptotic cells in the developing human cornea.
- To identify distinct developmental stages based on cell dynamics.
Main Methods:
- Examined corneal, limbal, and conjunctival sections from 11 weeks gestation to 6 months postnatal.
- Localized proliferating cells using proliferating cell nuclear antigen-like immunoreactivity (PCNA-LI).
- Detected apoptotic cells via terminal transferase-mediated nick-end labeling (TUNEL).
Main Results:
- Negligible proliferation before 17 weeks gestation.
- Widespread proliferation observed from 20 to 28 weeks gestation, including central and peripheral cornea.
- Proliferation declined after 28 weeks, confined to limbus and conjunctiva by 6 months postnatal.
- Apoptotic cells were absent before 38 weeks gestation, appearing in conjunctiva and cornea by 6 months postnatal.
- Limbus remained devoid of apoptotic cells throughout development.
Conclusions:
- Human cornea development involves three distinct phases: minimal proliferation, peak proliferation, and declining proliferation with apoptosis.
- The limbus serves as a stem cell niche, maintaining proliferative capacity while the central cornea undergoes differentiation and apoptosis.
- These findings provide a foundational map of corneal epithelial development.
Abstract:
To determine the distribution of proliferating and apoptotic cells in the human cornea during prenatal and early postnatal development, we examined sections of the bulbar conjunctiva, the limbus as well as the central and peripheral cornea between 11 weeks of gestation and 6 months after birth. The objective was to localize dividing cells by proliferating cell nuclear antigen-like immunoreactivity (PCNA-LI) and apoptotic cells by terminal transferase-mediated nick-end labeling (TUNEL). Before the 17th gestational week, PCNA-LI was absent in all 4 regions examined, indicating negligible cell proliferation during early development. After 20 weeks, strong PCNA-labeling was observed in all regions examined suggestive of high proliferative activity not only in the limbus and the bulbar conjunctiva, but also in the central and peripheral cornea. This rise in proliferative activity was followed by a steady decline: after 28 weeks, anti-PCNA staining gradually disappeared 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 picture described for the adult cornea. TUNEL-positive cells were virtually absent in all 4 regions examined before the 38th gestational week. Apoptotic cells only started to appear at 38 weeks; at this stage, they were confined to the bulbar conjunctival epithelium. At 6 months after birth, TUNEL-positive cells were observed in the bulbar conjunctival epithelium and the entire cornea; the limbus, however remained devoid of apoptotic cells throughout the entire prenatal and early postnatal period. The present study for the first time localizes proliferating and apoptotic cells in the epithelium of the developing human cornea. Three stages of development can be distinguished: Minimal proliferation (until 17th week), vigorous proliferation over 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.