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Editors Selection IGR 8-2

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Comment by Michael Fautsch on:

59479 Induced pluripotent stem cells restore function in a human cell loss model of open-angle glaucoma, Abu-Hassan DW; Li X; Ryan EI et al., Stem Cells, 2015; 33: 751-761

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TM cells play an essential role in IOP homeostasis by sensing changes in the outflow pathway. Reduction in TM cell number is believed to be a factor that contributes to loss of IOP regulation in POAG. However, this has not been examined experimentally until now. In the study by Abu-Hassan et al., the investigators observed that cultured human anterior segments have an IOP homeostatic response, returning IOP to normal following manual elevation of pressure by increasing the flow rate. They developed a model in human anterior segment cultures where TM cell number can be artificially reduced using saponin, a natural detergent found in many plants. In this cell depletion model, the investigators showed that reduction of TM cell number inhibited the anterior segment cultures ability to adjust outflow resistance to pre-elevated IOP levels. The investigators went one step farther and showed that reseeding the cell depletion cultures with primary TM monolayer cells repaired the cultures ability to restore normal pressure following a pressure elevation challenge. Non-TM cells such as human umbilical vein endothelial cell (HUVEC) or embryoid bodies from induced pluripotent stem cells (iPSCs) were ineffective in a similar study. The investigators also differentiated human iPSCs into TM-like cells, confirming their likeness by the presence of several markers that are present in mature TM cells, but not in iPSCs such as CHI3L1, Wnt1, %alpha;3 integrin and Aqp1. Functionally, the TM-like cells were phagocytic like mature TM cells. Similar to primary human TM cells, these iPSC derived TM-like cells also repopulated the TM and restored IOP homeostasis. These findings provide valuable information regarding the ability to establish TM-like cells from iPSCs and functionally perform similar activities to mature TM cells. This study is potentially seminal in the fact that the investigators have shown convincingly that TM cells are essential to maintaining IOP homeostasis.

The investigators have shown convincingly that TM cells are essential to maintaining IOP homeostasis

In addition, the ability to differentiate iPSCs cells into TM-like cells and show these cells are also capable of maintaining IOP homeostasis provides strong evidence that development of cell based strategies to treat POAG are feasible. Future studies to define culture based methods to reproducibly differentiate iPSCs to TM cells are warranted as this technology will enable clinicians to utilize autologous transplantation, since iPSCs can be derived from skin fibroblasts.

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