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Vivien Jane Coulson-Thomas, Tarsis Ferreira Gesteira, Lung-Kun Yeh, Amanda Nash, Yvette May Coulson- Thomas, Vincent Hascall; The limbal stem cell microenvironment regulates limbal stem cell differentiation. Invest. Ophthalmol. Vis. Sci. 2017;58(8):1383.
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© ARVO (1962-2015); The Authors (2016-present)
Limbal stem cells (LSCs), which are located in the basal layer of the corneal epithelium in the corneal limbus, play a vital role in maintaining the cornea. LSCs have a high capacity of self-renewal with increased potential for error-free proliferation and poor differentiation. LSCs also play an important role in preventing conjunctival epithelial cells from migrating onto the surface of the cornea. To date limited research has focused on unveiling the composition of the limbal stem cell niche, and, more importantly, the role the specific stem cell niche may play in LSC differentiation and function. Our work unveils the precise composition of the extracellular matrix (ECM) in the LSC niche and how it regulates LSC differentiation and function.
Immunofluorescence was used to characterize the composition of the ECM in the LSC niche in mouse cornea and this data was then confirmed through Western Blot analysis of extracted proteins from the corneal limbus. Thereafter, knock-out mouse models for key components in the LSC niche were used to unveil the importance of the niche in LSC differentiation and function.
Our data demonstrate that a specialized HA matrix is present in the limbal stem cell niche. Moreover, the composition of this ECM in the LSC niche is drastically different to that of the ECM in the rest of the corneal epithelium. Interestingly, upon insult to the cornea the composition of HA matrix in the LSC niche changes. Our preliminary data also show that knocking out key components of the HA matrix from the LSC niche alters LSC specification and leads to a decrease in the number of LSCs. These knock-out mice also present increased inflammation after injury.
The LSC niche is composed of a specialized HA ECM which differs from that present in the rest of the corneal epithelium. The precise composition of the LSC niche plays an important role in regulating LSC specification and function. Moreover, upon injury changes occur to the composition of the LSC niche, which could play a role in supporting the increase in LSC proliferation and migration after injury.
This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.
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