Researchers identify a promising new strategy for glaucoma cell replacement therapy

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Glaucoma is one of the leading causes of blindness worldwide, and vision loss due to damage to retinal ganglion cells (RGCs), is currently not reversible with any treatment. Some studies have looked at RGC replacement by cell transplantation, but this process is still in the research and development phase and has been plagued with limitations that highlight the need for more precise methods to effectively restore these cells to the retina. Now, a multidisciplinary team led by researchers at the Schepens Eye Research Institute of Mass. Eye and Ear has identified a promising new technique for glaucoma cell replacement therapy.

In their new study, the researchers altered the eye’s microenvironment in a way that enabled them to take stem cells from the blood and turn them into retinal ganglion cells capable of migrating and surviving in the retina. They conducted their research on the retinas of adult mice, but the results of the work could one day be applied to human retinas, according to researchers who published their results on Nov. 6. Proceedings of the National Academy of Sciences of the United States of America (PNAS).

A limitation that hinders the success of current stem cell transplantation techniques in retinal research is that most donor cells remain at the injection site and do not migrate to where they are most needed. To identify an improved solution, the researchers generated RGCs from stem cells, then tested the ability of different signaling molecules known as chemokines to direct these new neurons to their proper locations within the retina. The research team used a “big data” approach and examined hundreds of molecules and receptors to find 12 unique to RGCs. They were the best performing molecules for both stromal derived factor 1 transfer and replacement.

This method of using chemokines to stimulate the movement and integration of donor cells represents a promising approach for restoring vision in glaucoma patients. “It has been an exciting journey to work with a team of talented scientists with unique expertise in this research to develop novel strategies to modulate the local environment to guide cell behavior – strategies that could potentially be applied to the treatment of other neurodegenerative conditions.”

Petr Baranov, MD, PhD, senior author of Mass Eye & Year, is an assistant professor of ophthalmology at Harvard Medical School.

The study was co-led by members of Baranov’s lab at Maas I and Kahn, including bioengineer and lead study author Jonathan R. Soci, PhD, and lead bioinformatician Emil Kryukov, MD.

In addition to Baranov, Susi, and Kryukov, the study’s co-authors include Levi Todd, Monichan Fa, Volha V. Includes Malechka, John Deron Rivera, and Thomas A. Reh.

The research was funded by several National Eye Institute (NEI) grants from the National Institutes of Health (NIH) – a full list can be found in the paper – and grants from the Bright Focus Foundation and the Gilbert Family Foundation.

The University of Washington has published a patent covering the endogenous reprogramming technology described in this report with inventors LT and TAR.


Journal Reference:

Susey, J.R., etc. (2023). Controlling neuronal migration and maturation in the donor and neonatal eye through microenvironment engineering. PNAS.

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