The cornea is a tissue of unusual symmetry and optical clarity. Maintaining its structure and clarity is essential for high quality vision. Its exposed location makes it susceptible to wounding by physical insults, chemicals and UV radiation (UVR). Chronic exposure to UVR can cause diseases, including pterygia and ocular squamous neoplams. The corneal epithelium is derived from stem cells located in the limbus, a transitional zone epithelium at the cornea-conjunctiva boundary.

We devised an object-oriented mathematical simulation model and a complementary lineage tracing mouse model to investigate homeostasis of the corneal epithelium and its response to UVR damage (1,2). The biological model uses the K14CreERT2-Confetti line, and intravital fluorescence imaging to trace clonal lineages. We have used these models to show that corneal epithelial cells can self-organize into a cohesive, centripetal growth pattern without signals from other cells or the extracellular matrix. Only 3 conditions are needed: the location of stem cells in the limbus, a limited number of transit amplification cell divisions, and mobility in response to population pressure.

We examined the response of corneas to wounding by UVR and showed that the increased rate of centripetal migration that results can be explained by a reduction in the potential number of cell divisions of each epithelial clone. We also addressed the paradoxical ability of tissue transplanted from the central cornea being able to sustain long-term corneal epithelial growth in recipient eyes, despite the location of stem cells in the limbus. We showed that stem cell leakage from the limbal stem cell niche into the cornea can account for this ability.

This combination of intravital lineage tracing and object-oriented simulation model is a powerful methodology for investigating the mechanisms underlying the biology and pathology of epithelial tissues.