Abstract
The human cornea requires a smooth, transparent, robust and renewable surface to maintain its key optical and protective functions. The corneal epithelium is maintained by a local population of “stem cells”, which although not truly pluripotent, are capable of self-regeneration by asymmetric division. These cells are located at the limbus - the region where the conjunctiva-covered sclera meets the cornea. The widely accepted “XYZ” hypothesis of corneal epithelial maintenance postulates that limbal stem cells give rise to transient amplifying cells, which migrate and mature in both a centripetal and anterograde fashion towards the corneal surface. Many diseases and injuries to the limbus can cause the loss of this vital reservoir of cells and, due to subsequent surface irregularity and loss of corneal transparency, result in severe visual impairment, including blindness. Indeed, in some regions of the developing world corneal blindness may be more prevalent than cataract blindness. Such corneal blindness was previously irreversible, but over the past 30 years it has been possible to improve or restore vision using limbal “stem cell” transplants. Pioneering techniques required large tissue grafts that could compromise the donor eye, but recent developments allow the harvesting, ex-vivo expansion and transplantation of limbal stem cells from relatively small biopsies. In this review we outline limbal stem cell physiology in health and disease, describe our surgical approach to limbal stem cell deficiency, illustrate results of this intervention in our practice, and consider current and future advances in this arena.
Highlights
Blindness due to corneal disease is second only to cataract in causing visual loss world-wide[1]
The widely accepted “XYZ” hypothesis of corneal epithelial maintenance postulates that limbal stem cells give rise to transient amplifying cells, which migrate and mature in both a centripetal and anterograde fashion towards the corneal surface
In end-stage disease, the corneal epithelium is unable to regenerate due to loss of the “stem” cells that reside at the junction between cornea and conjunctiva
Summary
Blindness due to corneal disease is second only to cataract in causing visual loss world-wide[1]. A variety of diseases can cause corneal scarring, including chemical or thermal burns, inflammatory or autoimmune pathologies, connective tissue diseases, and infections such as trachoma (Table 1). These conditions can all result in progressive corneal opacification and replacement of the corneal epithelium with conjunctival epithelium. To maintain the healthy ocular surface, limbal stem cells resident within the palisades of Vogt, replicate and migrate centripetally as corneal basal epithelial cells, which mature and migrate to the ocular surface prior to shedding (Figure 1).
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