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The dynamics and destiny of corneal epithelial stem cells

22 November 2017
Research imagery on the cover of Stem Cell Reports

The cornea, the transparent structure of the front of the mammalian eye, is accountable for approximately two-thirds of the eye’s total optical power; it is essential for vision. In a study led by Professor Nick Di Girolamo, the dynamics and destiny of epithelial stem cells was observed in real-time in live animals using minimally invasive microscopy platforms, significantly improving our understanding of corneal development in humans.

Professor Nick Di Girolamo is the Director of Ocular Diseases Research and the head of Head, Mechanisms of Disease and Translational Research at the University of New South Wales. The paper, titled “Keratin-14-Positive Precursor Cells Spawn a Population of Migratory Corneal Epithelia that Maintain Tissue Mass throughout Life” was the cover article for the October edition of Stem Cell Reports.

Visualizing the generation and maintenance of the corneal epithelium in a living organism, especially in real-time, is a challenging endeavour. The cornea forms during the last major event of eye genesis. In mammals, the pre-corneal epithelium forms from surface ectoderm and comprises a dual layer of elongated, undifferentiated cells that are protected by the enveloping eyelids. Following eyelid opening, the corneal epithelium is exposed to external stimuli, including oxygen, particulate matter and microbes and mechanical forces from blinking. The combination of stimuli trigger cellular expansion from two to six layers as required to protect the eye. The development is incredibly specialised and ensures the cornea remains transparent and curved such that vision is not affected. How epithelial stem cells contribute to this formation and maintenance of the cornea is explored in this study.

Using transgenic mice, the fate or destiny of epithelial stem cells was followed in real-time. Using intra-vital microscopy, the formation of fluorescent radial stripes that emerged from the peripheral structure called the limbus, and migrated toward the central cornea was observed, demonstrating that the progenitor cells are designated early and widely distributed in the embryonic cornea.

The mechanism for both age-related clonal expansion and the formation of a central mid-line was established, thereby providing new insights into the basic biology of the mammalian corneal epithelium. The investigations also verified the concept that the corneal epithelium is immature at birth and develops progressively during post-natal life.

This study is also the first to report in a mammalian system, the biphasic (two-phase) nature of corneal epithelial development.

These findings are significant on three levels. Firstly, they deliver an accurate visual fate-map of corneo-limbal stem cells and their life-long clonal activity. Secondly, they provide mechanistic explanations for age-related patterns within the epithelium over time, using both in vivo and in silico investigations.

Lastly, these results provide the foundations of a model that can be used to interrogate perturbations of the cornea, including wound-healing, infection, and transplantation. Future studies will have profound implications for understanding the basic biology of the cornea and for devising new strategies to treat corneal diseases.

Congratulations Nick and the team. 

Stem Cell Reports is the official journal of the ISSCR and is published by Cell Press. The International Society for Stem Cell Research (ISSCR) is a non-profit, scientific membership organization providing a platform for professional and public education and the promotion of rigorous scientific and ethical standards in stem cell research and regenerative medicine.

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Read the journal article.