Burman and Sangwan stromal microenvironment called the stem cell niche, which consists of certain extracellular matrix components, cell membrane associated molecules, and cytokine dialogues (Watt and Hogan 2000). They may be activated on demand for tissue regeneration to increase their own population or to differentiate into transient amplifying cells (TAC), which are located in the corneal basal epithelium (Figure 1). On the contrary, TAC have a limited proliferating capacity with a short life span and are rapid cycling (Lehrer et al 1998). The limbal basal epithelial cells express the keratin pair K5/K14, like most of the undifferentiated cells of the strati- ﬁed epithelia but are devoid of the cornea-speciﬁc keratin pair K3/K12 (Schermer et al 1986). Limbal stem cell deﬁciency Limbal stem cells or the niche in which they reside can be compromised by a variety of insults leading to what is clinically known as limbal stem cell deﬁciency (LSCD). LSCD is characterized by conjunctivalization of the cornea (conjunctival epithelial ingrowth), vascularization, chronic inﬂammation, and poor epithelial integrity that manifests as irregular corneal surface, recurrent erosion, persistent epithelial defects and ﬁbrous ingrowth (Figure 2) (Anderson et al 2001). Limbal stem-cell deﬁciency can be primary, related to an insufﬁcient stromal microenvironment to support stem cell function, such as aniridia, congenital erythrokerato-dermia, keratitis associated with multiple endocrine deﬁciencies, neurotrophic (neural and ischaemic) keratopathy and chronic limbitis; or secondary (more common) related to external factors that destroy limbal stem cells such as chemical (most common) or thermal injuries, SJS, ocular cicatricial pemphigoid (OCP), multiple surgeries or cryotherapies, contact lens wear, or extensive microbial infection (Potten and Morris 1988; Tseng 1989; Kruse 1994; Pﬁster 1994; Dua 1995). Corneal stem-cell deﬁciency can be diffuse (total) or sectoral (partial) (Figure 3). In the latter case conjuncti- valisation of the corneal epithelium affects only part of the corneal surface. In some patients, limbal deﬁciency may be subclinical at the time of the insult, and may eventually progress to an overt stage of limbal deﬁciency as the stem cell population depletes further, over time (Dua et al 1994). If the conjunctival stem cells (presumed to be in the fornices) are also depleted, which is rare because of the larger area Conjunctiva LIMBUS CORNEA Peripheral Goblet Cells Proliferative compartment Basal Cells SC Differentiative Compartment Suprabasal Cell TCA Central PMC TDC TDC PMC Figure 1 Schematic diagram explaining the steps involved in proliferation and differentiation of limbal stem cells. Abbreviations: PMC, post-mitotic cells; SC, stem cells; TAC, transient amplifying cells; TDC, Terminally differentiated cells. 490 Clinical Ophthalmology 2008:2(3)