Review
Copyright ©2014 Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Sep 26, 2014; 6(4): 391-403
Published online Sep 26, 2014. doi: 10.4252/wjsc.v6.i4.391
Limbal stem cells: Central concepts of corneal epithelial homeostasis
Jinny J Yoon, Salim Ismail, Trevor Sherwin
Jinny J Yoon, Salim Ismail, Trevor Sherwin, Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Auckland 1020, New Zealand
Author contributions: Yoon JJ, Ismail S and Sherwin T contributed equally to writing this paper; Yoon JJ performed the literature searches, drafted and formatted the manuscript; Ismail S contributed to the writing of the manuscript, preparation of figures, literature searches and bibliography compilations; while Sherwin T contributed to review conception, writing of the manuscript, editing, analysis and formatting.
Supported by Save Sight Society New Zealand and Auckland Medical Research Foundation
Correspondence to: Trevor Sherwin, PhD, Associate Professor, Department of Ophthalmology, Faculty of Medical and Health Sciences, University of Auckland, Private Bag 92019, Auckland 1020, New Zealand. t.sherwin@auckland.ac.nz
Telephone: +64-9-9236466 Fax: +64-9-3677173
Received: July 25, 2014
Revised: August 20, 2014
Accepted: August 30, 2014
Published online: September 26, 2014
Processing time: 62 Days and 1.8 Hours
Abstract

A strong cohort of evidence exists that supports the localisation of corneal stem cells at the limbus. The distinguishing characteristics of limbal cells as stem cells include slow cycling properties, high proliferative potential when required, clonogenicity, absence of differentiation marker expression coupled with positive expression of progenitor markers, multipotency, centripetal migration, requirement for a distinct niche environment and the ability of transplanted limbal cells to regenerate the entire corneal epithelium. The existence of limbal stem cells supports the prevailing theory of corneal homeostasis, known as the XYZ hypothesis where X represents proliferation and stratification of limbal basal cells, Y centripetal migration of basal cells and Z desquamation of superficial cells. To maintain the mass of cornea, the sum of X and Y must equal Z and very elegant cell tracking experiments provide strong evidence in support of this theory. However, several recent studies have suggested the existence of oligopotent stem cells capable of corneal maintenance outside of the limbus. This review presents a summary of data which led to the current concepts of corneal epithelial homeostasis and discusses areas of controversy surrounding the existence of a secondary stem cell reservoir on the corneal surface

Keywords: Limbal stem cell; Corneal epithelium; XYZ hypothesis; Corneal homeostasis; Corneal wound repair

Core tip: It is a long held belief that stem cells reside only at the limbus. However, there are recent reports that present evidence of corneal repair and maintenance independent of limbal involvement. These findings call to light the possibility of previously undiscovered reservoirs of corneal stem/progenitor cells located at the central and peripheral cornea. A new secondary reservoir of stem cells has a significant clinical implication as new therapeutics for corneal degenerative disorders. This review outlines the historic evidence for limbal stem cells and discusses the role of these putative central and peripheral corneal stems cells in corneal homeostasis.