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

Xiaochen Fan, Emine K. Bilir, Olivia A. Kingston, Rachel A. Oldershaw, Victoria R. Kearns, Colin E. Willoughby, Carl M. Sheridan

Research output: Contribution to journalReview articlepeer-review

9 Citations (Scopus)
47 Downloads (Pure)

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.
Original languageEnglish
Article number1371
JournalBiomolecules
Volume11
Issue number9
Early online date16 Sept 2021
DOIs
Publication statusPublished (in print/issue) - 16 Sept 2021

Bibliographical note

Funding Information:
Acknowledgments: Grant funding; Carl Sheridan Glaucoma UK, St Pauls Eye Appeal; Emine Bilir, Republic of Turkey Ministry of National Education; Olivia Kingston is supported by a studentship from the MRC Discovery Medicine North (DiMeN) Doctoral Training Partnership (MR/R015902/1); Xiaochen Fan, GREAT Scholarships 2018—China campaign.

Funding Information:
Funding: This research was funded by Grant funding; Carl Sheridan and Colin Willoughby Glaucoma UK (formerly International Glaucoma Asscociation), St Pauls Eye Appeal; Emine Bilir, Republic of Turkey Ministry of National Education; Olivia Kingston is supported by a studentship from the MRC Discovery Medicine North (DiMeN) Doctoral Training Partnership (MR/R015902/1); Xiaochen Fan, GREAT Scholarships 2018—China campaign.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • trabecular meshwork
  • glaucoma
  • cellular transplantation
  • stem cells
  • iPSC
  • MSCs
  • Glaucoma
  • Trabecular meshwork
  • IPSC
  • Stem cells
  • Cellular transplantation
  • Humans
  • Biomarkers/metabolism
  • Animals
  • Intraocular Pressure/physiology
  • Trabecular Meshwork/cytology
  • Stem Cells/cytology

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