Evaluating alternative stem cell hypotheses for adult corneal epithelial maintenance

Area of Science:

• Ophthalmology
• Cell Biology
• Stem Cell Biology

Background:

• The corneal epithelium is essential for vision and ocular surface integrity.
• Understanding corneal epithelial maintenance is crucial for treating eye diseases and injuries.
• Several hypotheses exist regarding the origin and regulation of corneal epithelial cells.

Purpose of the Study:

• To review and evaluate evidence for competing hypotheses of corneal epithelial maintenance.
• To critically assess the limbal epithelial stem cell (LESC) hypothesis, the corneal epithelial stem cell (CESC) hypothesis, and a third proliferation-based model.
• To determine which hypothesis is most supported by current scientific evidence.

Main Methods:

• Literature review and critical analysis of published experimental evidence.
• Comparison of the predictive power of different hypotheses against observed data.
• Evaluation of evidence discriminating between the LESC and CESC hypotheses.
• Discussion of lineage-tracing experiments and their implications.

Main Results:

• The third hypothesis, involving proliferation without stem cells, is inconsistent with most evidence.
• Both the LESC and CESC hypotheses explain significant portions of the data but face specific challenges.
• Lineage-tracing studies increasingly support the LESC hypothesis, restricting stem cells to the limbus.
• Evidence suggests basal corneal cells may possess progenitor capacity, particularly when limbal stem cell function is impaired.

Conclusions:

• The LESC hypothesis is currently favored, supported by lineage-tracing data.
• The CESC hypothesis's concept of basal corneal cells acting as reserve progenitors remains relevant.
• A comprehensive understanding likely integrates aspects of both LESC and CESC models, acknowledging potential plasticity in corneal stem cell function.