Abstract
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.
Highlights
IntroductionIncreased outflow resistance in the conventional outflow pathway of the eye occurs at the trabecular meshwork (TM) in primary open-angle glaucoma (POAG) [2,3,4]
Glaucoma is characterised by an irreversible optic neuropathy, and elevated intra ocular pressure (IOP) is a major risk factor; reducing IOP is the primary treatment in the management of glaucoma
In 1982, Raviola et al first identified a new cell type in Schwalbe’s line. This fourth region of the trabecular meshwork (TM) does not filter aqueous humour, and evidence suggests that stem cells or stem-like progenitor cells reside in this area and that these cells are able to replace TM cells when damage occurs [7,25,26,27]
Summary
Increased outflow resistance in the conventional outflow pathway of the eye occurs at the trabecular meshwork (TM) in primary open-angle glaucoma (POAG) [2,3,4]. In POAG, increased resistance to outflow of aqueous humour at this structure coincides with altered extracellular matrix (ECM). Biomolecules 2021, 11, 1371 production, remodeling and stiffness, and a decrease in its cellularity [8,9]. A potential therapeutic strategy in POAG is repopulation of TM cells, which may compensate for the decreased cellularity in the glaucomatous TM, modify the abnormal ECM, and result in a reduction in IOP [7,10]. The complexity of the existing ECM architecture in both health and disease undoubtedly influences cellular behavior in repair, replacement, and regenerative scenarios. This review outlines the work to date on these approaches and discusses the progress and the challenges that accompany them
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