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Title: Soluble factors in the limbal niche : the role of Wnt signalling in the limbal response to corneal wounding
Author: Seyed-Safi, Ashkon Gideon
ISNI:       0000 0005 0288 5508
Awarding Body: UCL (University College London)
Current Institution: University College London (University of London)
Date of Award: 2020
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Limbal function is a key determinant of corneal epithelial integrity, with limbal epithelial stem cells (LESCs) responsible for corneal epithelial homeostasis. LESCs also exhibit an ability to respond to injury and mount regenerative response to corneal epithelial injury. LESCs are enriched within a specific microenvironment known as the stem cell niche and a combination of niche factors are involved in preserving the LESC phenotype and their ability to drive repair of the corneal surface. Clinically, loss of a functional LESC pool results in limbal stem cell deficiency (LSCD), a sight-threatening condition involving the inability to maintain the corneal epithelium, that currently requires the transplantation of LESCs. A greater understanding of factors within the niche will be important not only for improving outcomes of transplantation, but also for the development of new therapeutic strategies that look to reconstruct the limbal niche and restore the LESC population. This thesis presents the development of a validated and optimised porcine ex vivo corneal organ culture wounding model in which the response of LESCs to epithelial damage can be studied. The work presented in this thesis lends greater support to the view that, as with many other adult stem cell populations, Wnt signalling and the canonical ß-catenin dependent pathway in particular represent important regulators of LESC phenotype and function. It also presents the novel finding that in response to central corneal epithelial injury, DKK1 expression is transiently reduced in the limbus, and therefore may represent a key coordinator in altering the ß-catenindependent transcriptional activity of LESCs and progenitors in the basal limbal epithelium, and the increased levels of proliferation among these cells in response to central epithelial debridement.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available