Regulating the internal pressure of the eyeball (known as the “intraocular pressure” or IOP) is crucial for the health of the eye. Failure to maintain a healthy IOP can lead to vision loss in glaucoma. However, a new set of experiments by Dr. Markus Kuehn and his colleagues at the Iowa City Veterans Affairs Medical Center and the University of Iowa has shown that infusions of stem cells could help restore proper drainage for plugged-up eyes that are at risk for glaucoma.
Kuehn and his coworkers injected stem cells into the eyes of laboratory mice suffering with glaucoma. These infused cells regenerated the tiny, fragile patch of tissue known as the trabecular meshwork, which functions as a drain for the eyes. When fluid accumulates in the eye, the increase in IOP can lead to glaucoma. Glaucoma damages the optic nerve leads to blindness.
“We believe that replacement of damaged or lost trabecular meshwork cells with healthy cells can lead to functional restoration following transplantation into glaucoma eyes,” Kuehn wrote on his lab’s website. One potential advantage of the approach is that induced pluripotent stem cells (iPSCs) could be created from cells harvested from a patient’s own skin. That gets around the ethical problems with using fetal stem cells. It also lessens the chance of the patient’s body rejecting the transplanted cells.
In order to differentiate iPSCs into trabecular meshwork (TM) cells, Kuehn’s team cultured the iPSCs in medium that had previously been “conditioned” by actual human trabecular meshwork cells. Injection of these TM cells into the eyes of laboratory rodents led to a proliferation of new endogenous cells within the trabecular meshwork. The injected stem cells not only survived in the eyes of the animals, but also induced the eye into producing more of its own TM cells, thus multiplying the therapeutic effect.
Glaucoma has robbed some 120,000 Americans of their sight, according to data provided by the Glaucoma Research Foundation. African-Americans are at especially high risk, as are people over age 60, those with diabetes, and those with a family history of the disease. Glaucoma can be treated with medicines, but is not curable. Management of the disease can delay or even prevent the eventual loss of vision. Among the treatments used are eye drops and laser or traditional surgery.
Kuehn and his team think that their findings show some promise for the most common form of glaucoma, known as primary open angle glaucoma. It remains unclear if this mouse model is as relevant for other forms of the disease. Another possible limitation of this research is that the new trabecular meshwork cells generated from the stem cell infusion eventually succumb to the same disease process that caused the breakdown in the first place. This would require re-treatment and it is unclear whether an approach requiring multiple treatments over time would be viable. Kuehn and others to continue investigate this potentially fruitful approach.
This paper was published in the journal Proceedings of the National Academy of Sciences: Wei Zhu et al., “Transplantation of iPSC-derived TM cells rescues glaucoma phenotypes in vivo,” Proceedings of the National Academy of Sciences, 2016; 113 (25): E3492 DOI: 10.1073/pnas.1604153113.