Stem cells hold promise for restoring, replacing RPE, RGCs

SEATTLE – In the field of posterior segment disease, stem cells can be used to motivate endogenous repair or keep what you have left healthy and surviving, according to Jeffrey Goldberg, MD, PhD, here at the American Academy of Optometry’s plenary session.

Jeffrey Goldberg

He said a number of unmet needs exist in glaucoma: “better IOP-lowering approaches, treatments beyond reducing pressure, saving cells that haven’t died yet, replacing cells that have died (through stem cell therapy) and neuroenhancement (taking the dysfunctional cells and giving them a booster shot to enhance their function, thereby restoring visual function).

“We can inject almost any donor cells into the eye as long as they will secrete these growth factors and keep alive whatever we have left,” he said.

Stem cells are looked upon for taking over the function of the retinal pigment epithelium (RPE) at the back of the eye, Goldberg said, but the process is not as easy for retinal ganglion cell (RGC) therapy.

“We’re focusing on the inner portion of the retina, where we’re trying to get RGC transplants to replace the function of the RGC,” he said. “If we took stem cells out of the equation and skipped the problem of getting a stem cell to turn into a RGC, what if we take an actual RGC and transplant it into the retina? We do these cell transplants, and initially after an intravitreal injection, we see the cells layer over the surface. But if we give them some time, some of the cells actually do migrate into the ganglion cell layer where they’re supposed to live. These transplanted cells extend the neurites; they do some of the things they’re supposed to do.”

Goldberg said he has studied survival, migration and neurite growth.

“In almost all metrics, the stem cell-derived RGCs did almost as well as the transplanted RGCs,” he said.

“We are interested in not just whether they look like they’re going to the right place, but how they’re performing,” he continued. “Primary RGCs were able to receive about twice as many synapses as the stem cell-derived RGCs. These stem-cell derived RGCs are not fully functional. This raises questions. How do we tell a stem cell to be a functionally better RGC?”

Goldberg said progress is being made in the area of turning stem cells into ganglion cells.

He said it is not possible to use embryonic human tissue for this purpose, but induced fluripotent stem cells from the skin may be differentiated into retinal progenitor-type cells.

“If we overexpressed the certain transcription factors we need, can we get them to turn into RGCs?” he asked. “Ciliary margin cells are generating photoreceptors from RGC, amacrine cells and glia in culture.

“We may be able to replace the whole retina at some point,” Goldberg continued. “This approach could yield therapeutic value in the end.”

The plenary session was partially sponsored by Primary Care Optometry News.