The limbal epithelium of the eye – A review of limbal stem cell biology, disease and treatment

Abstract

The limbus is a narrow band of tissue that encircles the cornea, the transparent 'window' into the eye. The outermost layer of the cornea is the epithelium, which is necessary for clear vision. The limbus acts as a 'reservoir' for limbal stem cells which maintain and regenerate the corneal epithelium. It also functions as a barrier to the conjunctiva and its blood vessels. Limbal stem cell deficiency is a general term for diseases which are characterised by the impairment of the limbus, limbal stem cells and their ability to replenish the corneal epithelium through proliferation and differentiation. Consequently, sufferers experience chronic pain and progressive blindness. This paper will highlight the salient milestones of limbal stem cell biology and potential future treatments for limbal stem cell deficiency.

Ocular Toxicity of Chemical Warfare Agents

“…The limbal niche is highly vascularized, and factors that regulate niche function are delivered via multiple sources, including systemic circulation, tear film, AH, support cells in the LESC niche, keratocytes in the stroma, and corneal epithelial cells. Adverse conditions, such as chemical injury or persistent inflammation, can disrupt niche function, leading to a constellation of symptoms known as limbal stem cell deficiency (LSCD; Ahmad, 2012;Osei-Bempong et al, 2013). Dysregulation of the LESC niche has severe consequences for the corneal epithelium, which in turn evokes symptoms of corneal failure, such as invasion of goblet cells from the conjunctiva into the cornea, neovascularization, chronic inflammation, recurrent corneal erosions, keratitis, corneal ulceration, and stromal scarring.…”

Potential Role of Induced Pluripotent Stem Cells (IPSCs) for Cell-Based Therapy of the Ocular Surface

“…These cells help to maintain corneal transparency by actively pumping water out of the stroma [1]. The corneal epithelium has a key role in keeping the cornea transparent and free of blood vessels and, to this end, presents permanent repair phenomena essential for the conservation of the cornea’s physiology [1,2,3]. The homeostasis of the corneal epithelium is crucial to maintaining the structural integrity of the ocular surface, the transparency of the cornea and visual function.…”

“…The human limbus—the circumferential anatomic area (approximately 1.5 mm wide) that separates the clear cornea from the opaque sclera, which is covered by conjunctiva—serves as the “reservoir” for the stem cells and also provides a barrier to the overgrowth of conjunctival epithelial cells and its blood vessels onto the cornea [1,2,3] (Figure 1). Due to their particularities, the limbal stem cells (LSCs) have a crucial role in maintaining the integrity and in the renewal events of corneal epithelium.…”

“…In the limbus, it is possible to identify several cell subpopulations of different progenies (typical progenitors and amplifying cells at different stages of differentiation), melanocytes, antigen-presenting and mesenchymal cells, vascular elements and nerve endings that form a specialized and unique environment called niche . This particular microenvironment is considered responsible for the proliferative and self-renewal cellular characteristics of the limbal region [2,3,6]. The LSC niche is an anatomically defined area that is thought to provide a variety of factors, such as physical protection, survival factors and cytokines and is deemed essential to the maintenance of the “stemness” of the stem cell population while preventing entry into differentiation [2,6].…”

Special Series: Transplantation of Stem Cells into the Eye

“…Cornea is the transparent front of the eye, which together with the lens ensures that light entering the eye is focused onto the retina. Transparency of the cornea is ensured through continuous regeneration of corneal epithelium via corneal epithelial stem cells residing at the limbus (also known as limbal stem cells or LSCs) and perfectly organized stromal keratocytes; however, dysfunction in these processes can lead to corneal opacity affecting up to 8 million people worldwide [1]. The search for LSC markers has been an ongoing quest for the last 20 years, resulting in the identification of but a handful of markers of which not all have been proven to mark specific stem or progenitor cell populations [2].…”