advertisement

Glaucoma Dialogue IGR 16-3

Response

Comment by Mary Kelley 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

Find related abstracts

We would like to thank Dr. Weinreb and the IGR editorial team for selecting our paper for discussion and the reviewers for their thoughtful and generous comments recognizing the therapeutic potential of patient-specific stem cells for IOP control in glaucoma.

We should clarify a few points mentioned by the reviewers, which are very relevant to outflow pathway biology and to glaucoma, but were perhaps unclear since they were not the central focus of this stem cell restoration study aimed at a broader audience.

First, in all of these flow studies, saponin treatment, which removed approximately 30% of outflow pathway cells, did not directly change the outflow facility or the outflow resistance. Immediately after perfusion pressures were increased from 1x to 2x for saponin-treated or controls, outflow facility was not different, i.e., doubling the perfusion pressure doubled the outflow rate.

Second, with the functional cells present, either in the controls, which had not been saponin- treated, or with TM or TM-like iPS added back, the 2x pressure challenge triggered a slow increase in the outflow facility, and therefore a decrease in the outflow resistance, which only became apparent and significant after at around 24 hours. This is the classic IOP homeostatic response that we have described in detail in a recent review.1 In this review, we argued that the ability of outflow pathway cells to sense pressure elevations and to respond by adjusting the outflow resistance to restore the IOP to within a narrow acceptable range is the reason that most people do not ever develop glaucoma.

We interpret these two observations to mean: 1) that outflow pathway cells are not the outflow resistance, since their presence or absence does not change outflow facility. This supports the idea that juxtacanalicular extracellular matrix provides most of the outflow resistance; and 2) a sufficient number of functional TM and/or Schlemm’s canal inner wall endothelial cells are absolutely essential to regulate and maintain the outflow resistance over time within acceptable IOP ranges.

Since it can be argued that the loss of an active functional IOP homeostatic response is a hallmark of most of glaucoma, we think these studies argue for the relevance of the observation by Alvarado, et. al., that outflow pathway cell loss is increased in glaucoma.²

• ← Previous
• Next →