Maintenance of the corneal epithelium is essential for vision and is a dynamic process incorporating constant cell production, movement and loss. Although cell-based therapies involving the transplantation of putative stem cells are well advanced for the treatment of human corneal defects, the scientific understanding of these interventions is poor. No definitive marker that discriminates stem cells that maintain the corneal epithelium from the surrounding tissue has been discovered and the identity of these elusive cells is, therefore, hotly debated. The key elements of corneal epithelial maintenance have long been recognised but it is still not known how this dynamic balance is co-ordinated during normal homeostasis to ensure the corneal epithelium is maintained at a uniform thickness. Most indirect experimental evidence supports the limbal epithelial stem cell (LESC) hypothesis, which proposes that the adult corneal epithelium is maintained by stem cells located in the limbus at the corneal periphery. However, this has been challenged recently by the corneal epithelial stem cell (CESC) hypothesis, which proposes that during normal homeostasis the mouse corneal epithelium is maintained by stem cells located throughout the basal corneal epithelium with LESCs only contributing during wound healing. In this chapter we review experimental studies, mostly based on animal work, that provide insights into how stem cells maintain the normal corneal epithelium and consider the merits of the alternative LESC and CESC hypotheses. Finally, we highlight some recent research on other stem cell systems and consider how this could influence future research directions for identifying the stem cells that maintain the corneal epithelium.
|Title of host publication||Mouse Development|
|Subtitle of host publication||From Oocyte to Stem Cells|
|Number of pages||38|
|Publication status||Published - 12 Oct 2012|
|Name||Results and Problems in Cell Differentiation|
We thank Ronnie Grant for assistance with illustrations, Dr Alan W. Flake and Molecular Therapy for permission to reproduce images shown in Fig. 19.4e, f and Dr Takayuki Nagasaki and Molecular Vision for permission to reproduce images shown in Figs. 19.4c,d and 19.7o,p. We also thank Developmental Dynamics, BMC Developmental Biology, Investigative Ophthalmology & Vision Science and Molecular Vision for permission to reproduce our own previously published images included in Figs 19.4 and 19.7. We are grateful to the Wellcome Trust, Medical Research Council, Biotechnology and Biological Sciences Research Council, Fight for Sight (UK), the RS MacDonald Charitable Trust and the Royal College of Surgeons of Edinburgh for support for our own research.