Abstract
The protective function and transparency provided by the corneal epithelium are dependent on and maintained by the regenerative capacity of limbal epithelial stem cells (LESCs). These LESCs are supported by the limbal niche, a specialized microenvironment consisting of cellular and non-cellular components. Disruption of the limbal niche, primarily from injuries or inflammatory processes, can negatively impact the regenerative ability of LESCs. Limbal stem cell deficiency (LSCD) directly hampers the regenerative ability of the corneal epithelium and allows the conjunctival epithelium to invade the cornea, which results in severe visual impairment. Treatment involves restoring the LESC population and functionality; however, few clinically practiced therapies currently exist. This review outlines the current understanding of the limbal niche, its pathology and the emerging approaches targeted at restoring the limbal niche. Most emerging approaches are in developmental phases but show promise for treating LSCD and accelerating corneal regeneration. Specifically, we examine cell-based therapies, bio-active extracellular matrices and soluble factor therapies in considerable depth.
Highlights
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations
The damaged cornea can have persistently increased levels of cytokines and other inflammatory mediators, such as interferon-γ, IL-1α, IL-1β, IL-6 and vascular endothelial growth factor (VEGF), which disrupt the conditions needed for the limbal epithelial stem cells (LESCs) to proliferate [9,10]
Inflammation can cause pathological changes in the extracellular matrix of the limbus, such as increased vascular and lymphatic vessel formation [12]. This leads to abnormal density and morphology of LESCs through decreased extra cellular matrix (ECM) adhesiveness and altered expression of stem cell markers [12,13]
Summary
Genetic, or immunologic disturbances to the cornea can disrupt the limbal niche microenvironment, resulting in limbal stem cell deficiency (LSCD). The damaged cornea can have persistently increased levels of cytokines and other inflammatory mediators, such as interferon-γ, IL-1α, IL-1β, IL-6 and vascular endothelial growth factor (VEGF), which disrupt the conditions needed for the LESCs to proliferate [9,10] This inflammatory milieu leads to recruitment of T-lymphocytes, neutrophils and macrophages to the site of injury, which can disrupt the LESC niche [11]. Inflammation can cause pathological changes in the extracellular matrix of the limbus, such as increased vascular and lymphatic vessel formation [12] This leads to abnormal density and morphology of LESCs through decreased extra cellular matrix (ECM) adhesiveness and altered expression of stem cell markers [12,13]. While many of the strategies are just beginning to reach the clinic, they represent promising advancements in restoring the limbal niche
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
