Regenerative capacity of the corneal transition zone for endothelial cell therapy
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Regenerative capacity of the corneal transition zone for endothelial cell therapy Nicole Ming Sie1,2, Gary Hin-Fai Yam1,3* , Yu Qiang Soh1,2, Matthew Lovatt1, Deepinder Dhaliwal3, Viridiana Kocaba1,4 and Jodhbir S. Mehta1,2,5,6*
Abstract The corneal endothelium located on the posterior corneal surface is responsible for regulating stromal hydration. This is contributed by a monolayer of corneal endothelial cells (CECs), which are metabolically active in a continuous fluid-coupled efflux of ions from the corneal stroma into the aqueous humor, preventing stromal overhydration and preserving the orderly arrangement of stromal collagen fibrils, which is essential for corneal transparency. Mature CECs do not have regenerative capacity and cell loss due to aging and diseases results in irreversible stromal edema and a loss of corneal clarity. The current gold standard of treatment for this worldwide blindness caused by corneal endothelial failure is the corneal transplantation using cadaveric donor corneas. The top indication is Fuchs corneal endothelial dystrophy/degeneration, which represents 39% of all corneal transplants performed. However, the global shortage of transplantable donor corneas has restricted the treatment outcomes, hence instigating a need to research for alternative therapies. One such avenue is the CEC regeneration from endothelial progenitors, which have been identified in the peripheral endothelium and the adjacent transition zone. This review examines the evidence supporting the existence of endothelial progenitors in the posterior limbus and summarizes the existing knowledge on the microanatomy of the transitional zone. We give an overview of the isolation and ex vivo propagation of human endothelial progenitors in the transition zone, and their growth and differentiation capacity to the corneal endothelium. Transplanting these bioengineered constructs into in vivo models of corneal endothelial degeneration will prove the efficacy and viability, and the long-term maintenance of functional endothelium. This will develop a novel regenerative therapy for the management of corneal endothelial diseases. Keywords: Cornea endothelium, Corneal endothelial progenitors, Schwalbe’s line, transitional zone, corneal endothelial cell degeneration The cornea is the transparent anterior part of the eye and is composed of five different layers. The outermost layer is the corneal epithelium, followed by Bowman’s membrane, corneal stroma, Descemet’s membrane (DM), and the innermost corneal endothelium. The adult human cornea is about 550 μm thick and serves 3 * Correspondence: [email protected]; [email protected] 1 Tissue Engineering and Cell Therapy Group, Singapore Eye Research Institute, 20 College Road, The Academia, Discovery Tower Level 6, Singapore 169856, Singapore Full list of author information is available at the end of the article
major functions: (1) as a mechanical and chemical barrier to protect the inner ocular tissues, (2) as a transparent medium for light passage, and (3) light
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