Human Trabecular Meshwork Progenitors

Zhu, Qin; Zhang, Yuan; Tighe, Sean; Liu, Yongsong; Zhu, Yingting; Hu, Min

doi:10.7150/ijms.32089

Cited by 5 publications

(3 citation statements)

References 66 publications

(94 reference statements)

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“…This region does not filter aqueous humor into the Schlemm's canal but contains cells expressing stem cell and neural crest markers (ABCG2, myc, nestin, p75 NTR , N-cadherin). These cells have been demonstrated to undergo multipotent differentiation into corneal endothelial cells, adipocytes, and chondrocytes, but not osteocytes or keratocytes [59,60] (Table 1). However, no data has been provided on whether the TM-derived endothelial-like cells could display specific physiological activities, i.e., pumping function and trans-endothelial resistance.…”

Section: Corneal Endothelial Periphery and Transition Zonementioning

confidence: 99%

Regenerative capacity of the corneal transition zone for endothelial cell therapy

et al. 2020

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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 over-hydration 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.

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Section: Corneal Endothelial Periphery and Transition Zonementioning

confidence: 99%

Regenerative capacity of the corneal transition zone for endothelial cell therapy

et al. 2020

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“…These components create a hydrated, negatively charged, BM-like ECM, composed of laminin, fibronectin, collagen type IV, proteoglycans and hyaluronic acid (HA) [ 23 , 49 , 50 , 51 ]. An important trait of TM cellular functionality, is their inherent plasticity to differentiate into different cell types, with the characteristics the cells display being highly dependent on the biochemical and biophysical cues they are exposed to, an aspect that will influence the development of a TM or JCT model [ 28 , 52 , 53 , 54 , 55 ]. It is thought that the JCT cells exhibit fibroblast/myofibroblast features ( Figure 1 D), which can transition into a predominantly endothelial/phagocytic phenotype within the UVM/CSM sections ( Figure 1 E) [ 28 ].…”

Section: Tm and Esc Biological Propertiesmentioning

confidence: 99%

“…This has led other studies to look deeper into the manipulation of TM cells through topographical features, with electrospun, non-aligned, nano-fibrous scaffolds containing poly L-lactic acid/polycaprolactone improving the differentiation of TM cells into glial and neural progenitor cells [ 97 ]. In addition to the embedding of TM cells into Matrigel ® , a BM mixture that is rich in nanotopographical features [ 101 ] was deemed favourable for the expansion and manipulation of human TM cells into adipocytes, chondrocytes and endothelial cells [ 52 , 53 ].…”

Section: Current Biomaterials Approaches To Modelling the Tm/escmentioning

confidence: 99%

Fundamental Biomaterial Considerations in the Development of a 3D Model Representative of Primary Open Angle Glaucoma

et al. 2021

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Glaucoma is a leading cause of irreversible blindness globally, with primary open angle glaucoma (POAG) being the most common subset. Raised intraocular pressure is an important risk factor for POAG and is caused by a reduction in aqueous humour (AqH) outflow due to dysfunctional cellular and matrix dynamics in the eye’s main drainage site, the trabecular meshwork (TM) and Schlemm’s canal (SC). The TM/SC are highly specialised tissues that regulate AqH outflow; however, their exact mechanisms of AqH outflow control are still not fully understood. Emulating physiologically relevant 3D TM/S in vitro models poses challenges to accurately mimic the complex biophysical and biochemical cues that take place in healthy and glaucomatous TM/SC in vivo. With development of such models still in its infancy, there is a clear need for more well-defined approaches that will accurately contrast the two central regions that become dysfunctional in POAG; the juxtacanalicular tissue (JCT) region of the TM and inner wall endothelia of the Schlemm’s canal (eSC). This review will discuss the unique biological and biomechanical characteristics that are thought to influence AqH outflow and POAG progression. Further consideration into fundamental biomaterial attributes for the formation of a biomimetic POAG/AqH outflow model will also be explored for future success in pre-clinical drug discovery and disease translation.

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Revisiting Existing Evidence of Corneal Endothelial Progenitors and Their Potential Therapeutic Applications in Corneal Endothelial Dysfunction

Meir

Chen

et al. 2020

Adv Ther

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Human Trabecular Meshwork Progenitors

Cited by 5 publications

References 66 publications

Regenerative capacity of the corneal transition zone for endothelial cell therapy

Regenerative capacity of the corneal transition zone for endothelial cell therapy

Fundamental Biomaterial Considerations in the Development of a 3D Model Representative of Primary Open Angle Glaucoma

Revisiting Existing Evidence of Corneal Endothelial Progenitors and Their Potential Therapeutic Applications in Corneal Endothelial Dysfunction

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