Abstract
Purpose :
Studying ocular surface stem and progenitor cell dynamics in homeostasis and injury
Methods :
We performed lineage tracing experiments using R26R-Confetti mice to follow K14+ corneal/conjuncival basal epithelial cells stochastically induced to express one out of four fluorescent genes. A long-term live-imaging experiments in living animal allowed following clonal dynamics under homeostasis and following limbal or corneal injuries
Results :
In hemostasis, radial limbal stripes of slow migrating cells proceeded toward the corneal center were observed and the turnover of this process was about 4 months. Corneal cells, however, significantly contributed to mild corneal wound repair while large limbal streaks appeared within a week following severe corneal wounding that coincided with partial loss of corneal transparency.
Following controlled alkali burn to the limbus, total corneal opacity, neovascularization, and corneal scarring was developed in most animals, coinciding with large stripes of cells occasionally emerging from the conjunctiva and reaching the center of the cornea. Interestingly, mice lacking pigmentation, were less responsive to K14-promoter transgenic induction and displayed a more severe response to injury as compared to their black pigmented littermates, suggesting that they may have a lower regenerative potential.
Conclusions :
This study shows unequivocally that the limbus is the major if not only source of long-term corneal regeneration under homeostasis. Following limbal destruction by alkali burn, cojunctival stripes ingrowth coincided with clinical deterioration. In conclusion, this model may be efficiently used for better understanding of the mechanisms of corneal regeneration in homeostasis and may aid to developing novel strategies for therapy.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.