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Editors Selection IGR 15-1

Novel and experimental therapies: Stem cells

Comment by Jeffrey Goldberg on:

52639 Stem cells from trabecular meshwork home to TM tissue in vivo, Du Y; Yun H; Yang E et al., Investigative Ophthalmology and Visual Science, 2013; 54: 1450-1459

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There are a number of important opportunities to explore whether stem cells may change the treatment of glaucoma. Of course there is considerable focus on the use of stem cells for retinal ganglion cell replacement therapy, a tall order but an important goal, and for retinal ganglion cell neuroprotection, as many stem cell populations secrete numerous factors that promote survival and even regeneration of neurons. Less well-documented, but perhaps more tractable when considering a clinical path to translation, is the premise of transplanting stem cells to the trabecular meshwork ™. What would stem cells do in the TM? One key hypothesis for intraocular pressure elevation relevant to glaucoma risk involves the loss of cellularity, or at least of stem cells, from the TM. Excessive accumulation of extracellular matrix and other proteins or debris, whether inside or adjacent to the TM cells, may lead to loss of cellularity, and a concomitant inability to remodel the meshwork and keep the flow high and pressure low. Indeed some of our current therapies including selective laser trabeculoplasty are thought to work through stimulation of endogenous stem cells to remodel this outflow pathway. Now, Du and colleagues have taken another important step towards translating this into human use. They cultured human trabecular meshwork stem cells with a fluorescent dye and demonstrated that there is a population of these cells proliferating fast enough to consider them stem (or really, progenitor) cells, but slowly enough to keep the fluorescent marker. They then injected these cells, or a fibroblast cell control injection, into the anterior chamber of mice. Compared to the fibroblasts, the trabecular meshwork progenitor cells demonstrated a preferential localization at the meshwork, as opposed to the fibroblasts, which scattered to the iris and cornea as well.

If these cells are injected in a model of ocular hypertension, can they lower IOP and prevent glaucomatous damage?

The authors interpreted this as preferential homing, although preferential survival or preferential proliferation at the TM were not ruled out. Future work including a more detailed quantification of cell numbers by localization will be a welcome addition to the micrograph pictures provided. Finally, the authors demonstrate no increase in IOP in response to the cell injection, leaving another exciting question to follow: if these cells are injected in a model of ocular hypertension, can they lower IOP and prevent glaucomatous damage?

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