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Trabecular meshwork restoration in primary open-angle glaucoma using stem cells

Author(s):

Lin Cheng

Wei Zhu

Lauren K. Wareham

Emmanuel S. Buys

Marcus H. Kuehn

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Abstract:

The trabecular meshwork (TM) plays a critical role in maintaining appropriate intraocular pressure (IOP) in the eye. The tissue is populated by specialized cells that are crucial for its function. The number of these TM cells declines with age and is particularly low in individuals with primary open-angle glaucoma (POAG), a disease that is frequently associated with TM dysfunction and elevated IOP. A number of laboratories have begun to investigate whether stem cell replacement of lost or damaged TM cells can functionally regenerate the tissue and restore IOP control. Toward this goal, mesenchymal stem cells (MSC), trabecular meshwork stem cells (TMSC), induced pluripotent stem cells (iPSC), and iPSC-derived TM-like cells (iPSC-TM) have been injected into the eye. Many of the studies report functional improvements, such as a decline in IOP.
The choice of experimental model is not trivial and ideally findings can be repeated in multiple animal models. For example, transplantation of iPSC-TM into the eyes of myocilinY437H transgenic mice restores outflow facility and decreases IOP, which can also be observed when these cells are transplanted into the eyes of guanylyl cyclase-1 knockout mice (GC1-/-) with elevated IOP. Transplantation increases the number of cells observed in the TM and findings suggest that the increase is at least partly due to the propensity of MSC and iPSC-TM to engender proliferation of the eye’s endogenous TM cells.
These recent findings are encouraging and suggest that restoration of the TM cellularity by stem cell transplantation may be a reliable approach to treat TM degeneration due to a variety of etiologies. This, in turn, suggests a therapeutic potential of regenerating the TM in many POAG cases with elevated IOP.

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