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 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.

Highlights

  • They show reduced expression of pluripotency markers Nanog, Oct4, and Sox2, which is important in assessing if these cells can give rise to a tumor in vivo. This co-culture method of induced pluripotent stem cells (iPSCs)-trabecular meshwork (TM) induction was successful when human iPSCs derived from dermal fibroblasts and keratinocytes were cultured with human primary TM cells [29]. We described another method of creating iPSC-TM cells from human iPSCs following a two-step induction process, where iPSCs are first induced into neural crest cells (NCC) and TM-like cells [31]

  • Stem cell transplantation for TM regeneration remains an important area for exploring new effective glaucoma treatment options

  • Many different types of stem cells can be used in TM regeneration, and it seems they work in similar, but distinct ways

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Summary

Willoughby and Carl Sheridan

Glaucoma is one of the leading causes of vision loss and complete blindness in the world today especially in African and Western countries affecting over 60 million people [1]. This reduction of IOP is currently achieved via a variety of ways, including drug therapies and surgical interventions. Since glaucoma is a degenerative disease, where TM and RGC cellularity is decreased [11,12], using stem cells to regenerate tissue is a promising area of study to explore more efficient and long-term treatment for glaucoma. Transplantation of stem cells, both pluripotent and multipotent, or differentiated functional cells from stem cells, in degenerative diseases is an encouraging area of study because of their regenerative and malleable characteristics. Pluripotent and multipotent stem cells have been studied in the context of both RGC and TM regeneration [16,17]. We will focus on the use of TM stem cells in TM regeneration, and touch on the use of other types of stem cells in TM regeneration for glaucoma

Cell-Based Therapies for Trabecular Meshwork Regeneration by Using Trabecular
Main Findings
Mechanisms of Cell Mediated Glaucoma Treatment
Conclusions
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