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.

中文翻译：

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小梁网细胞的更换——眼压控制的前路？

青光眼是全球视力丧失的主要原因之一，其特征是不可逆的视神经损伤和进行性视力丧失。原发性开角型青光眼 (POAG) 是青光眼的一个子集，以正常的前房角和升高的眼压 (IOP) 为特征。降低眼压是治疗POAG的主要可改变因素，而小梁网（TM）是房水流出（AH）和流出阻力的主要部位。TM 的结构和组成是其调节 AH 流出功能的关键。在自然衰老过程中发现的 TM 细胞的功能障碍和丢失，在 POAG 中更是如此，可导致异常的细胞外基质 (ECM) 积累、TM 硬度增加和 IOP 增加。所以，TM 的结构和功能的修复或再生被认为是 POAG 的潜在治疗方法。细胞移植是在 POAG 中重新填充 TM 细胞的一种有吸引力的选择，但要开发一种细胞替代方法，仍然需要解决各种挑战。细胞替代的选择包括自体或同种异体方法，这导致了对 TM 祖细胞、诱导多能干细胞 (iPSCs) 和间充质干细胞 (MSCs) 作为潜在干细胞来源候选者的研究。然而，祖细胞和 TM 细胞群的潜在可塑性和缺乏明确的细胞标志物使生物学挑战更加复杂。位于 TM 不同区域的 TM 细胞的形态和差异基因表达可能会导致不同的细胞替代或再生方法。像这样，这篇综述描述了迄今为止研究不同细胞来源及其不同细胞分离和分化方法所采取的不同方法。此外，我们强调了如何在不同的动物和离体模型系统中评估这些方法，以及这些方法在未来 POAG 治疗中的潜力。