Abnormal corneal epithelial wound healing in partial-thickness removal of limbal epithelium. To explain this distribution of stem cells and the different roles played by stem cells in different zones of the eye, the researchers propose that the expanding epithelia of the cornea and the conjunctiva act like tectonic plates, squeezing the limbus between them into a kind of equilibrium zone. As the outermost layer of the eye, the cornea both serves as a barrier and provides the essential optical function of transmitting light to the retina.

In the case of inflammation or wounding, however, the stromal keratocytes become activated and mitotic. Br J Ophthalmol, Margo, C.E. Limbal basal epithelial cells are described as β1 integrin bright as are the stem cells of the epidermis suggesting a gradient of expression that decreases with differentiation. Ultraviolet B-induced mitochondrial dysfunction is associated with decreased cell detachment of corneal epithelial cells in vitro.

Management of aniridic keratopathy with keratolimbal allograft: a limbal stem cell transplantation technique. Piatigorsky, J. Azuara-Blanco, A. Gupta, P. (2000). Expression of the 55-kD/64-kD corneal keratins in ocular surface epithelium. Daughter transient amplifying cells (TACs) divide and migrate towards the central cornea (arrowed) to replenish the epithelium, which rests on Bowman's layer (BL).
The basal cells also regulate organisation of hemidesmonsomes and focal complexes to maintain attachment to the underlying basement membrane. Adams, G.B. He, H. Chen, S.Y.

(1971). Lavker, R.M. Exp Eye Res, Schlotzer-Schrehardt, U. Kruse, F.E. The phenotype of the activated keratocytes changes to resemble that of fibroblasts and myofibroblasts, and connective tissue matrix secreted by these cells during wound-healing becomes opaque scars. Schwartz, G.S. The remaining mesenchymal cells between these two layers differentiate into corneal stromal fibroblasts (Cintron et al., 1983). Piatigorsky, J.

Gortzak-Moorstein, N. (2003). Djalilian, A.R. Chen, Z. Yoon, K.C.

Kheirkhah, A. Tseng, S.C. (2007). The literature reflects many attempts to prospectively identify LESC using a specific marker. Proteoic analysis of soluble factors secreted by limbal fibroblasts. These putative stem cells are primitive and can divide symmetrically to self renew and asymmetrically to produce daughter transit amplifying cells (TAC) that migrate centripetally to populate the basal layer of the corneal epithelium (see Figure 3; Kinoshita et al., 1981; Tseng, 1989). Interestingly, hypoxic in vitro conditions have been found to produce larger, less differentiated limbal epithelial cell colonies suggesting that low oxygen levels may induce selective proliferation of undifferentiated cells (Miyashita et al., 2007).

et al.

Soluble vascular endothelial growth factor receptor-1 contributes to the corneal antiangiogenic barrier.

Throughout life, our self-renewing tissues rely upon populations of stem cells / progenitors to replenish themselves throughout life following normal wear and tear and injury.

(1997). Nature, Mann, I. (2000).

Implications of corneal epithelial migration, circadian rhythm, and suprabasally located DNA-sunthesising keratinocytes. Like other epithelia, the epithelium of the cornea is maintained by stem cells. Another important factor leading to progressive loss of vision is aniridic-related keratopathy (ARK; Mackman et al., 1979; Margo, 1983) which occurs in 90% of patients. This differs with humans, where there is a second wave of mesenchymal cell migration into the space between the newly formed endothelial layer and the surface ectoderm. A role for notch signalling in human corneal epithelial cell differentiation and proliferation. As a result of LESC deficiency conjunctivalisation, neovascularisation, chronic inflammation, recurrent erosions, ulceration and stromal scarring can occur causing painful vision loss (Holland and Schwartz, 1996; Kenyon and Tseng, 1989; Puangsricharern and Tseng, 1995). Location and clonal analysis of stem cells and their differentiated progeny in the human ocular surface. Later, mathematical analysis indicated that the corneal epithelial cell mass could be renewed by cells from the limbal epithelium alone (Sharma and Coles, 1989). This tissue is supported by a basement membrane overlying an acellular zone of connective tissue known as the Bowman layer. Prior 'Common Colds': Less Severe COVID-19? (1991). Silversides, D.W. Patel, K. Overbeek, P.A. (2007a). Surv Ophthalmol, Nishida, K. Kinoshita, S. Ohashi, Y. Kuwayama, Y. Yamamoto, S. (1995). Pax6SeyDey and Pax6SeyH mice have Pax6 gene deletions (Hill et al., 1991; Hogan et al., 1986; Lyon et al., 2000; Schmahl et al., 1993; Theiler et al., 1980). Development of Dickie's small eye: an early lethal mutation in the house mouse. 1 C) and is the residence for epithelial stem cells (SCs) that replenish aged corneal epithelial cells throughout life. Deficiencies in PAX6 leads to aniridia resulting in impaired corneal epithelial function and eventual LESC failure, which may be due to altered niche development. (1995). (2000). Questions? (2005). This research led to the discovery that the Pax6 gene was responsible for the Sey phenotype and suggested that it was also responsible for the human disease, aniridia (Hill et al., 1991). The stroma, a collagenous connective tissue, makes up 90% of the cornea. (2000). Sun, T.T. In the corneal epithelium, mitotically active basal cells continuously renew the nonmitotic population of suprabasal cells, which subsequently flatten as they migrate to the surface, where they are lost by desquamation. On the ultrastructure of the developing and adult mouse corneal stroma. Invest Ophthalmol Vis Sci. Pflugfelder, S.C. Li, D.Q. However, upregulation of α9 in wounded murine corneas have since indicated this integrin to be associated with TAC's (Stepp and Zhu, 1997). It consists of superficial squamous cells, central suprabasal cells and a single layer of inner columnar basal cells. Hypoxia enhances the expansion of human limbal epithelial progenitor cells in vitro. (1944). Galaxies Trapped: Supermassive Black Hole, 3D Printed Artificial Corneas Similar to Human Ones, Adhesive Gel Bonds to Eye Surface, Could Repair Injuries Without Surgery, Stem Cells May Help Improve Corneal Wound Healing, Researchers Find Proliferating Cells in Normal, Diseased Corneal Endothelium, Stroke Warning Signs Often Occur Hours Or Days Before Attack, Loss of Smell and Taste Validated as COVID-19 Symptoms in Patients With High Recovery Rate, Drink Coffee After Breakfast, Not Before, for Better Metabolic Control, Silk Fibers Improve Bioink for 3D-Printed Artificial Tissues and Organs, Mammals Share Gene Pathways That Allow Zebrafish to Grow New Eyes. At P28 the corneal epithelium is representative of the adult epithelium, with a single layer of columnar basal cells, which become flattened as they move to the surface. Expression of C/EBPΔ in a subset of LESC both in vivo and in vitro has recently been suggested to be involved in the regulation of self-renewal and LESC cell cycle length (Barbaro et al., 2007). (1991).
Other growth factors are produced by keratocytes in the supporting stroma (West-Mays and Dwivedi, 2006) and by the corneal epithelial cells themselves (Rolando and Zierhut, 2001). Ruskell, G.L. Curr Opin Ophthalmol, West-Mays, J.A.

(1970). Multipotent stem cells in human corneal stroma. For up to seven days of age the corneal and limbal epithelia in rats is 1–2 cells layers (Chung et al., 1992). Tseng, D.Y. (1983). Development, Robinson, M.L. Dennis, S. Khan, S. (2003). Furthermore, the complete removal of the limbus results in impaired corneal function, neovascularisation and conjunctival ingrowth (Huang and Tseng, 1991). J Cell Sci, Li, T. Lu, L. (2005). Different cell sized in human limbal and central corneal basal epithelia measured by confocal microscopy and flow cytometry.

Highly resistant tight junctions formed between neighbouring cells provide a protective barrier (Klyce, 1972). Horsburgh, G. Cohen, J. Hetherington, C.M. This forms after the optic vesicles come in contact with the surface ectoderm. Desmet, V. (1985). Characterisation of putative stem cell phenotype in human limbal epithelia. The cornea is comprised of five layers (see Figure 1), the outermost non-keratinised stratified epithelium, Bowman's layer, a highly ordered keratocyte-populated collagenous stroma, Descemet's membrane and the inner endothelium (a cellular monolayer). Thoft and Friend developed the ‘The X, Y, Z hypothesis of corneal epithelial maintenance’. Friend, J. Thoft, R.A. (1987). (2004). Bogani, D. Boyd, Y. Guillot, P. Favor, j. Down-regulation of Pax6 is associated with abnormal differentiation of corneal epithelial surface diseases. The limbus is already recognized as a source of cells for corneal stem cell therapy in humans, and this new research indicates that the cornea itself can also be explored as a potential source of these cells. Nature, Zhou, S. Schuetz, J.D.

In the event of a rupture in the equilibrium, such as a large corneal injury, these limbal stem cells migrate into the cornea and conjunctiva and differentiate into the appropriate cell type to make repairs. Even though the limbal epithelium is derived from the surface ectoderm a number of neural stem cell markers have been suggested as LESC markers. Biophys J, Miyashita, H. Higa, K. Kato, N. Kawakita, T. Yoshida, S. Tsubota, K. Shimmura, S. (2007). Although the surface of the cornea is exposed to atmospheric oxygen, the LESC niche lies beneath a number of cell layers where the oxygen tension is likely to be lower.

Could a Fecal Transplant One Day Be the Secret of Eternal Youth? Jamieson, S. Dickson, C. Overbeek, P.A. Friend, J. Thoft, R.A. (1988).

Kudoh, K. Cotsarelis, G. Sun, T.T. Using suppressive subtractive hybridisation, Sun et al., 2006 identified a novel gene (EEDA) with localisation to corneal basal and suprabasal cells, suggesting it is involved in early stage stratification of epithelial differentiation (Sun et al., 2006). Green, H. (1981). Human limbal epithelium contains side population cells expressing the ATP-binding cassette transporter, Watt, F.M. Sex chromatin of donor corneal epithelium in rabbits. Kays, W.T.

However, since these initial observations a number of reports have suggested that p63 is not sufficiently specific to act as an LESC marker as it has also been localised to basal cells of the peripheral and central cornea in humans (Chen et al., 2004; Dua et al., 2003) and in rats (Chee et al., 2006). Isoforms of DeltaNp63 and the migration of ocular limbal cells in human corneal regeneration. Biol Cell, Pei, Y.F.