Retinal neuron. Image: Dr_Microbe/iStock/Getty Images Plus
Researchers working with mice have identified a potential new strategy for replacing retinal ganglion cells to treat glaucoma, one of the leading causes of blindness worldwide.
There are currently no treatments to reverse vision loss due to death of retinal ganglion cells, or RGCs.
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The multidisciplinary team, led by Harvard Medical School researchers at the Schepens Eye Research Institute of Mass Eye and Ear, made the RGCs from blood stem cells.
In the study, published Nov 6. in PNAS, the researchers changed the microenvironment in the eye in a way that enabled them to take stem cells from blood and turn them into retinal ganglion cells capable of migrating and surviving into the eye’s retina.
They conducted their study on the adult mouse retina. If the findings are replicated in humans, the work could one day be applied to the human retina.
Cell replacement therapy
Some studies have looked at replacing RGCs through cell transplants, but this process, still in the research and development stage, is fraught with limitations. A more precise manner of effectively repopulating these cells in the retina is needed.
One limitation that prevents the success of current stem cell transplantation strategies in the retina is that the majority of donor cells remain at the site of injection and do not migrate where they are most needed.
To identify a better solution, the MEE team created RGCs out of stem cells, then tested the ability of various signaling molecules, known as chemokines, to guide these new neurons to their correct positions within the retina.
The researchers used a big data approach. They examined hundreds of such molecules and receptors to find 12 unique to RGCs. They found stromal derived factor 1 was the best-performing molecule for both migration and transplantation.
“This method of using chemokines to guide donor cell movement and integration represents a promising approach to restoring vision in glaucoma patients,” said senior author Petr Baranov, HMS assistant professor of ophthalmology at Schepens. “It was an exciting journey to work with a team of talented scientists with unique expertise to develop novel techniques to modify the local environment to guide cell behavior — techniques that potentially could be applied to treat other neurodegenerative conditions.”
The study was co-led by members of Baranov’s lab at Mass Eye and Ear, including bioengineer and lead study author Jonathan R. Soucy and lead bioinformatician Emil Kriukov.
Authorship, funding, disclosures
Additional authors included Levi Todd, Monichan Phay, Volha V. Malechka, John Dayron Rivera, and Thomas A. Reh.
The study was funded by the National Eye Institute of the National Institutes of Health, Bright Focus Foundation, and Gilbert Family Foundation.
The University of Washington discloses a patent incorporating the endogenous reprogramming technology described in this report with inventors Todd and Reh.
Adapted from a Mass Eye and Ear news release.
