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Biomolecules
Special Issues
Cellular Therapies for Glaucoma
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Cellular Therapies for Glaucoma

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Molecular Medicine".

Deadline for manuscript submissions: closed (1 June 2021) | Viewed by 23011

Special Issue Editors

Prof. Dr. Colin E. Willoughby

E-Mail Website
Guest Editor
Genomic Medicine Group, Biomedical Sciences Research Institute, Ulster University, Coleraine BT52 1SA, Northern Ireland, UK
Interests: microRNAs; ophthalmology; glaucoma; trabecular meshwork; fibrosis; oxidative stress; mitochondria; TGFβ; gene therapy
Special Issues, Collections and Topics in MDPI journals
Dr. Carl Sheridan

E-Mail Website
Guest Editor
Institute of Life Course and Medical Sciences, University of Liverpool, Liverpool L7 8TX, UK
Interests: pathobiology of eye disease; wound healing; tissue engineering; retina; cell-matrix interactions; cell transplant; ageing; trabecular meshwork; stem cell differentiation

Special Issue Information

Dear Colleagues,

Glaucoma is a chronic neurodegeneration of retinal ganglion cells and the leading cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG) is the commonest form of glaucoma. Lowering intraocular pressure (IOP) is the only modifiable risk factor in POAG to date. Elevated IOP results from several molecular and cellular alterations in the trabecular meshwork. Cell and stem cell-based therapies could offer the potential to repair the trabecular meshwork in restoring function. Despite lowering IOP, retinal ganglion cell loss can continue, and so, therapies are required to protect or restore RGC function. Cell-based therapies (stem cell or encapsulated cells) may offer the potential to provide RGC replacement, optic nerve regeneration or cell-mediated neuroprotection. Understanding the molecular biology of the TM and RGC may also support cell-based therapies for glaucoma in which specific cell-derived mediators (neurotrophic factors, miRNAs or extracellular vesicles) are used to restore or preserve function. In this Special Issue, we plan to cover the role of cell and molecular biology, stem cells, and tissue engineering to discuss the current status of cell-based approaches as therapies in glaucoma and the upcoming challenges from a multidisciplinary perspective.

Prof. Dr. Colin E. Willoughby
Dr. Carl Sheridan
Guest Editors

Manuscript Submission Information

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Keywords

  • glaucoma
  • trabecular meshwork
  • retinal ganglion cells
  • optic nerve
  • cell therapy
  • stem cells
  • tissue engineering
  • bioreactive molecules
  • bio-engineeering
  • microRNAs
  • extracellular vesicles
  • encapsulated cells

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Published Papers (5 papers)

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Review

17 pages, 329 KiB  
Review
Replacement of the Trabecular Meshwork Cells—A Way Ahead in IOP Control?
by Xiaochen Fan, Emine K. Bilir, Olivia A. Kingston, Rachel A. Oldershaw, Victoria R. Kearns, Colin E. Willoughby and Carl M. Sheridan
Biomolecules 2021, 11(9), 1371; https://doi.org/10.3390/biom11091371 - 16 Sep 2021
Cited by 9 | Viewed by 4723
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Cellular Therapies for Glaucoma)
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Graphical abstract

13 pages, 13821 KiB  
Review
Cell-Based Therapies for Trabecular Meshwork Regeneration to Treat Glaucoma
by Shayshadri Mallick, Malini Sharma, Ajay Kumar and Yiqin Du
Biomolecules 2021, 11(9), 1258; https://doi.org/10.3390/biom11091258 - 24 Aug 2021
Cited by 17 | Viewed by 3373
Abstract
Glaucoma is clinically characterized by elevated intraocular pressure (IOP) that leads to retinal ganglion cell (RGC) and optic nerve damage, and eventually blindness if left untreated. Even in normal pressure glaucoma patients, a reduction of IOP is currently the only effective way to [...] Read more.
Glaucoma is clinically characterized by elevated intraocular pressure (IOP) that leads to retinal ganglion cell (RGC) and optic nerve damage, and eventually blindness if left untreated. Even in normal pressure glaucoma patients, a reduction of IOP is currently the only effective way to prevent blindness, by either increasing aqueous humor outflow or decreasing aqueous humor production. The trabecular meshwork (TM) and the adjacent Schlemm’s canal inner wall play a key role in regulating IOP by providing resistance when aqueous humor drains through the tissue. TM dysfunction seen in glaucoma, through reduced cellularity, abnormal extracellular matrix accumulation, and increased stiffness, contributes to elevated IOP, but current therapies do not target the TM tissue. Stem cell transplantation for regeneration and re-functionalization of damaged TM has shown promise in providing a more direct and effective therapy for glaucoma. In this review, we describe the use of different types of stem cells for TM regeneration in glaucoma models, the mechanisms of regeneration, and the potential for glaucoma treatment using autologous stem cell transplantation. Full article
(This article belongs to the Special Issue Cellular Therapies for Glaucoma)
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Figure 1

14 pages, 910 KiB  
Review
Targeting the NLRP3 Inflammasome in Glaucoma
by Sophie Coyle, Mohammed Naeem Khan, Melody Chemaly, Breedge Callaghan, Chelsey Doyle, Colin E. Willoughby, Sarah D. Atkinson, Meredith Gregory-Ksander and Victoria McGilligan
Biomolecules 2021, 11(8), 1239; https://doi.org/10.3390/biom11081239 - 19 Aug 2021
Cited by 35 | Viewed by 5466
Abstract
Glaucoma is a group of optic neuropathies characterised by the degeneration of retinal ganglion cells, resulting in damage to the optic nerve head (ONH) and loss of vision in one or both eyes. Increased intraocular pressure (IOP) is one of the major aetiological [...] Read more.
Glaucoma is a group of optic neuropathies characterised by the degeneration of retinal ganglion cells, resulting in damage to the optic nerve head (ONH) and loss of vision in one or both eyes. Increased intraocular pressure (IOP) is one of the major aetiological risk factors in glaucoma, and is currently the only modifiable risk factor. However, 30–40% of glaucoma patients do not present with elevated IOP and still proceed to lose vision. The pathophysiology of glaucoma is therefore not completely understood, and there is a need for the development of IOP-independent neuroprotective therapies to preserve vision. Neuroinflammation has been shown to play a key role in glaucoma and, specifically, the NLRP3 inflammasome, a key driver of inflammation, has recently been implicated. The NLRP3 inflammasome is expressed in the eye and its activation is reported in pre-clinical studies of glaucoma. Activation of the NLRP3 inflammasome results in IL-1β processing. This pro inflammatory cytokine is elevated in the blood of glaucoma patients and is believed to drive neurotoxic inflammation, resulting in axon degeneration and the death of retinal ganglion cells (RGCs). This review discusses glaucoma as an inflammatory disease and evaluates targeting the NLRP3 inflammasome as a therapeutic strategy. A hypothetical mechanism for the action of the NLRP3 inflammasome in glaucoma is presented. Full article
(This article belongs to the Special Issue Cellular Therapies for Glaucoma)
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13 pages, 295 KiB  
Review
Stem Cell-Based Regeneration and Restoration for Retinal Ganglion Cell: Recent Advancements and Current Challenges
by Jingxue Zhang, Shen Wu, Zi-Bing Jin and Ningli Wang
Biomolecules 2021, 11(7), 987; https://doi.org/10.3390/biom11070987 - 5 Jul 2021
Cited by 18 | Viewed by 3708
Abstract
Glaucoma is a group of irreversible blinding eye diseases characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons. Currently, there is no effective method to fundamentally resolve the issue of RGC degeneration. Recent advances have revealed that visual function [...] Read more.
Glaucoma is a group of irreversible blinding eye diseases characterized by the progressive loss of retinal ganglion cells (RGCs) and their axons. Currently, there is no effective method to fundamentally resolve the issue of RGC degeneration. Recent advances have revealed that visual function recovery could be achieved with stem cell-based therapy by replacing damaged RGCs with cell transplantation, providing nutritional factors for damaged RGCs, and supplying healthy mitochondria and other cellular components to exert neuroprotective effects and mediate transdifferentiation of autologous retinal stem cells to accomplish endogenous regeneration of RGC. This article reviews the recent research progress in the above-mentioned fields, including the breakthroughs in the fields of in vivo transdifferentiation of retinal endogenous stem cells and reversal of the RGC aging phenotype, and discusses the obstacles in the clinical translation of the stem cell therapy. Full article
(This article belongs to the Special Issue Cellular Therapies for Glaucoma)
24 pages, 784 KiB  
Review
Use of Gene Therapy in Retinal Ganglion Cell Neuroprotection: Current Concepts and Future Directions
by Jess Rhee and Kendrick Co Shih
Biomolecules 2021, 11(4), 581; https://doi.org/10.3390/biom11040581 - 15 Apr 2021
Cited by 16 | Viewed by 4496
Abstract
We systematically reviewed published translational research on gene-based therapy for retinal ganglion cell (RGC) neuroprotection. A search was conducted on Entrez PubMed on 23 December 2020 using the keywords “gene therapy”, “retinal ganglion cell” and “neuroprotection”. The initial search yielded 82 relevant articles. [...] Read more.
We systematically reviewed published translational research on gene-based therapy for retinal ganglion cell (RGC) neuroprotection. A search was conducted on Entrez PubMed on 23 December 2020 using the keywords “gene therapy”, “retinal ganglion cell” and “neuroprotection”. The initial search yielded 82 relevant articles. After restricting publications to those with full text available and in the English language, and then curating for only original articles on gene-based therapy, the final yield was 18 relevant articles. From the 18 papers, 17 of the papers utilized an adeno-associated viral (AAV) vector for gene therapy encoding specific genes of interest. Specifically, six of the studies utilized an AAV vector encoding brain-derived neurotrophic factor (BDNF), two of the studies utilized an AAV vector encoding erythropoietin (EPO), the remaining 10 papers utilized AAV vectors encoding different genes and one microRNA study. Although the literature shows promising results in both in vivo and in vitro models, there is still a significant way to go before gene-based therapy for RGC neuroprotection can proceed to clinical trials. Namely, the models of injury in many of the studies were more acute in nature, unlike the more progressive and neurodegenerative pathophysiology of diseases, such as glaucoma. The regulation of gene expression is also highly unexplored despite the use of AAV vectors in the majority of the studies reviewed. It is also expected that with the successful launch of messenger ribonucleic acid (mRNA)-based vaccinations in 2020, we will see a shift towards this technology for gene-based therapy in glaucoma neuroprotection. Full article
(This article belongs to the Special Issue Cellular Therapies for Glaucoma)
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