Stem cell exosomes may help retinal ganglion cells survive

Stem cell secretions, or exosomes, may confer a protective benefit on retinal ganglion cells, according to a new animal model study from researchers at the National Eye Institute (NEI), published in the journal Stem Cells Translational Medicine. This discovery may pave the way for future potential therapies for glaucoma, one of the leading causes of blindness in the United States.

Ben Mead, PhD, post-doctoral fellow at NEI, and fellow researchers assessed the role of stem cell exosomes—small, membrane-enclosed packages formed intracellularly and then expelled, and thought to be part of the cellular disposal system—on retinal ganglion cells in a rat model of glaucoma, the axons of which form the optic nerve. Retinal ganglion cell death leads to the vision loss experienced by patients with glaucoma and other optic neuropathies.

Previous studies have shown that exosomes—which are filled with proteins, lipids, and gene-regulating RNA; aid in cell-to-cell interactions; and perform a signaling role—can be taken up from one cell by other cells via cell membrane fusion. This, in turn, induces the production of new proteins.

The transplantation of exosomes isolated from stem cells have some advantages over the transplantation of whole stem cells.

According to Mead: ““Exosomes can be purified, stored, and precisely dosed in ways that stem cells cannot.”

In addition, exosomes also offer the advantage of not having the risks associated with live stem cell transplantation into the eyes.

Using a rat glaucoma model, Mead and colleagues studied exosomes isolated from bone marrow stem cells on retinal ganglion cells. They injected exosomes weekly into rat vitreous after the cells were fluorescently labelled.

Untreated rats experienced a 90% loss of their retinal ganglion cells compared with an approximately 33% loss in the exosome-treated rats. Via electroretinography, researchers also found that the stem cell exosome-treated retinal ganglion cells retained their function.

More research is needed, however, to understand the specifics of this protective effect and about the specific contents of exosomes, according to co-author and NEI principal investigator, Stansilav Tomarev, PhD.

“We need to know which particular microRNA – there are more than 2,000 different microRNA molecules – are delivered into the retinal ganglion cells and what proteins or signaling pathways are being targeted upon arrival,” said Dr. Tomarev. “We also need to attempt to target exosomes to specific sets of neurons and other cell types or groups of cells,” he said, adding that the optimal approach of this potential therapy, including delivery and frequency, requires further study.

This work was supported by the Intramural Research Programs of the National Eye Institute.