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Corneal Epithelial Stem Cells and Their Therapeutic Application

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Abstract

The cornea is the clear window at the front of the eye and its clarity is vital for the transmission of light to the retina at the back of the eye for visual perception. The surface of the cornea is made up of an epithelium, which is continuous with that of the surrounding conjunctiva. The transition between the corneal and conjunctival epithelia is formed by the limbal epithelium. The limbal epithelium has two particular important functions. First, it harbours the corneal epithelial stem cells (CESCs), also known as limbal stem cells (LSCs). These stem cells (SCs) provide a reservoir for corneal epithelial cells, which are needed to replace those lost continuously from the corneal surface. Second, it acts as a barrier to prevent the phenotypically and functionally different conjunctival epithelium from encroaching onto the corneal surface, which would impair the transparency of the cornea and lead to visual loss.

LSC deficiency (LSCD) is a disease characterised by the loss or dysfunction of CESCs. It results from a variety of causes such as chemical or thermal burns, contact len–related eye disease, hereditary disorders (such as aniridia and ectodermal dysplasia), iatrogenic causes (such as surgery, radiotherapy, and cryotherapy), and inflammatory eye diseases (such as Stevens-Johnson’s syndrome and ocular cicatricial pemphigoid). In LSCD, the conjunctival epithelium and its underlying blood vessels encroach onto the surface of the cornea, resulting in significant visual impairment. Additionally, the corneal epithelium fails to heal normally, resulting in recurrent epithelial breakdown associated with constant pain and photophobia. The understanding of CESC biology and its clinical application has allowed the development of treatment strategies for this blinding and painful condition. The mainstay of treatment in severe LSCD is the transplantation of large pieces of healthy limbal tissue. This tissue can be obtained from the other eye of the patient (if healthy), or the healthy eye of a living related donor or cadaveric donor. Existing techniques are not ideal due to the quantity of tissue required and the additional need for immunosuppression in allograft recipients. Recently it has been proposed that much smaller pieces of limbal tissue containing CESCs can be cultured in the laboratory, and this ex vivo expanded tissue can then be transplanted to the eye with LSCD. In a significant number of with LSCD, the disease is total and bilateral, which precludes any expansion of existing CESCs. The possibility of using alternative autologous sources of epithelial SCs to regenerate the corneal surface is also now the subject of laboratory study and clinical application. Our knowledge of CESC biology is rapidly growing. However, to fully benefit from their therapeutic use, the ability to accurately identify them by specific marker expression and the ability to understand the exact nature of the cellular and molecular mechanisms that maintain their “stemness” is required. Once these markers have been identified and our understanding of the physiological processes involved in maintaining the SC niche are complete, the therapeutic implications will be vast.

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Kolli, S., Lako, M., Figueiredo, F., Ahmad, S. (2009). Corneal Epithelial Stem Cells and Their Therapeutic Application. In: Baharvand, H. (eds) Trends in Stem Cell Biology and Technology. Humana Press. https://doi.org/10.1007/978-1-60327-905-5_18

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