Replacement of the Trabecular Meshwork Cells—A Way Ahead in IOP Control?

Glaucoma is one of the leading causes of vision loss worldwide, characterised with irreversible optic nerve damage and progressive vision loss. Primary open-angle glaucoma (POAG) is a subset of glaucoma, characterised by normal anterior chamber angle and raised intraocular pressure (IOP). Reducing I...

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Main Authors: Xiaochen Fan, Emine K. Bilir, Olivia A. Kingston, Rachel A. Oldershaw, Victoria R. Kearns, Colin E. Willoughby, Carl M. Sheridan
Format: Article
Language:English
Published: MDPI AG 2021-09-01
Series:Biomolecules
Subjects:
Online Access:https://www.mdpi.com/2218-273X/11/9/1371
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author Xiaochen Fan
Emine K. Bilir
Olivia A. Kingston
Rachel A. Oldershaw
Victoria R. Kearns
Colin E. Willoughby
Carl M. Sheridan
author_facet Xiaochen Fan
Emine K. Bilir
Olivia A. Kingston
Rachel A. Oldershaw
Victoria R. Kearns
Colin E. Willoughby
Carl M. Sheridan
author_sort Xiaochen Fan
collection DOAJ
description Glaucoma is one of the leading causes of vision loss worldwide, characterised with irreversible optic nerve damage and progressive vision loss. Primary open-angle glaucoma (POAG) is a subset of glaucoma, characterised by normal anterior chamber angle and raised intraocular pressure (IOP). Reducing IOP is the main modifiable factor in the treatment of POAG, and the trabecular meshwork (TM) is the primary site of aqueous humour outflow (AH) and the resistance to outflow. The structure and the composition of the TM are key to its function in regulating AH outflow. Dysfunction and loss of the TM cells found in the natural ageing process and more so in POAG can cause abnormal extracellular matrix (ECM) accumulation, increased TM stiffness, and increased IOP. Therefore, repair or regeneration of TM’s structure and function is considered as a potential treatment for POAG. Cell transplantation is an attractive option to repopulate the TM cells in POAG, but to develop a cell replacement approach, various challenges are still to be addressed. The choice of cell replacement covers autologous or allogenic approaches, which led to investigations into TM progenitor cells, induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs) as potential stem cell source candidates. However, the potential plasticity and the lack of definitive cell markers for the progenitor and the TM cell population compound the biological challenge. Morphological and differential gene expression of TM cells located within different regions of the TM may give rise to different cell replacement or regenerative approaches. As such, this review describes the different approaches taken to date investigating different cell sources and their differing cell isolation and differentiation methodologies. In addition, we highlighted how these approaches were evaluated in different animal and ex vivo model systems and the potential of these methods in future POAG treatment.
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spelling doaj.art-b8171e80e4834d09be474cc80e11b8f92023-11-22T12:11:40ZengMDPI AGBiomolecules2218-273X2021-09-01119137110.3390/biom11091371Replacement of the Trabecular Meshwork Cells—A Way Ahead in IOP Control?Xiaochen Fan0Emine K. Bilir1Olivia A. Kingston2Rachel A. Oldershaw3Victoria R. Kearns4Colin E. Willoughby5Carl M. Sheridan6Department of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UKDepartment of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UKDepartment of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UKDepartment of Musculoskeletal and Ageing Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UKDepartment of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UKDepartment of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UKDepartment of Eye and Vision Science, Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L69 3BX, UKGlaucoma is one of the leading causes of vision loss worldwide, characterised with irreversible optic nerve damage and progressive vision loss. Primary open-angle glaucoma (POAG) is a subset of glaucoma, characterised by normal anterior chamber angle and raised intraocular pressure (IOP). Reducing IOP is the main modifiable factor in the treatment of POAG, and the trabecular meshwork (TM) is the primary site of aqueous humour outflow (AH) and the resistance to outflow. The structure and the composition of the TM are key to its function in regulating AH outflow. Dysfunction and loss of the TM cells found in the natural ageing process and more so in POAG can cause abnormal extracellular matrix (ECM) accumulation, increased TM stiffness, and increased IOP. Therefore, repair or regeneration of TM’s structure and function is considered as a potential treatment for POAG. Cell transplantation is an attractive option to repopulate the TM cells in POAG, but to develop a cell replacement approach, various challenges are still to be addressed. The choice of cell replacement covers autologous or allogenic approaches, which led to investigations into TM progenitor cells, induced pluripotent stem cells (iPSCs), and mesenchymal stem cells (MSCs) as potential stem cell source candidates. However, the potential plasticity and the lack of definitive cell markers for the progenitor and the TM cell population compound the biological challenge. Morphological and differential gene expression of TM cells located within different regions of the TM may give rise to different cell replacement or regenerative approaches. As such, this review describes the different approaches taken to date investigating different cell sources and their differing cell isolation and differentiation methodologies. In addition, we highlighted how these approaches were evaluated in different animal and ex vivo model systems and the potential of these methods in future POAG treatment.https://www.mdpi.com/2218-273X/11/9/1371trabecular meshworkglaucomacellular transplantationstem cellsiPSCMSCs
spellingShingle Xiaochen Fan
Emine K. Bilir
Olivia A. Kingston
Rachel A. Oldershaw
Victoria R. Kearns
Colin E. Willoughby
Carl M. Sheridan
Replacement of the Trabecular Meshwork Cells—A Way Ahead in IOP Control?
Biomolecules
trabecular meshwork
glaucoma
cellular transplantation
stem cells
iPSC
MSCs
title Replacement of the Trabecular Meshwork Cells—A Way Ahead in IOP Control?
title_full Replacement of the Trabecular Meshwork Cells—A Way Ahead in IOP Control?
title_fullStr Replacement of the Trabecular Meshwork Cells—A Way Ahead in IOP Control?
title_full_unstemmed Replacement of the Trabecular Meshwork Cells—A Way Ahead in IOP Control?
title_short Replacement of the Trabecular Meshwork Cells—A Way Ahead in IOP Control?
title_sort replacement of the trabecular meshwork cells a way ahead in iop control
topic trabecular meshwork
glaucoma
cellular transplantation
stem cells
iPSC
MSCs
url https://www.mdpi.com/2218-273X/11/9/1371
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AT rachelaoldershaw replacementofthetrabecularmeshworkcellsawayaheadiniopcontrol
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