The development of stem cell treatments for glaucoma faces big hurdles, but researchers are making rapid progress, said Yvonne Ou, MD.
Dr. Ou, assistant professor of ophthalmology, University of California, San Francisco (UCSF), outlined that progress at the Glaucoma 360 CME Symposium.
Stem cell therapy offers the tantalizing possibility of growing new retinal ganglion cells to repair the damage of glaucoma.
To reach that point, grafted cells must not only survive, but also differentiate into mature retinal ganglion cell subtypes. Researchers estimate that there are at least 20 subtypes. These cells must locate the correct area in the retina and integrate into it.
They must generate both efferent and afferent synapses. They must generate axons and find the right targets for these axons. They also must maintain a retinotopic map.
“It sounds like science fiction, for sure,” Dr. Ou said.
By comparison, in retinal degenerative diseases there are already animal models in which stem cells have been differentiated into photoreceptors and transplanted back into animals, restoring vision. To treat retinal degenerative diseases, researchers only have to replace a single type of cell with fewer connections necessary.
Still, Dr. Ou and others have made strides in creating functional retinal ganglion stem cells.
Stem cells for retinal ganglions can come from embryos, adult tissues including the retina, and reprogrammed cells. Dr. Ou focused on the third category.
Using a cocktail of transcription factors, researchers can induce skin fibroblasts to become pluripotent stem cells and program them as retinal ganglion cells, she said.
Future steps in research would include transplanting these cells back into animals. There they could be used in drug trials. Ultimately, they might be transplanted into humans.
Even in a laboratory setting, stem cells can create useful tissue for research purposes. Ganglion cells can be cultured with other cell types to provide information about interactions.
“You can actually generate a three-dimensional eye in a Petri dish,” Dr. Ou said. “And those could be used to study the interaction of ganglion cells with other cell types in a more native environment.”
One could potentially develop an entire optic nerve for study purposes as well, she said.
Dr. Ou and her colleagues at UCSF have themselves obtained skin biopsies from patients who have different types of glaucoma, and used them to generate pluripotent stem cells. They have differentiated these cells into ganglion-like cells, she said.
They have shown that these cells are generating synaptin and that they are capable of forming action potentials. They hope to generate axons and apply the cells to injuries, such as compressive injury.
In facing the hurdles ahead, Dr. Ou draws courage from noting how fast the field has already moved. The first stem cells were not isolated until 1998, she noted.
In 2006, researchers induced pluripotent stem cells. In the same year they derived retinal progenitors from human embryonic stem cells. Also that year, they transplanted mouse rod precursors into degenerating retinas to restore visual function.
In 2012, they created retinal ganglion cells that could generate axons the full length of the visual pathway.
And just last year, researchers successfully transplanted an induced pluripotent stem cell into an eye for the first time.
These crucial steps show the tremendous potential, she said.
“In the next decade or so we will be making great progress,” Dr. Ou said.