Glaucoma is one of the leading causes of blindness worldwide, and vision loss, due to the loss of retinal ganglion cells (RGCs), cannot currently be reversed by any treatment. Some studies have looked at replacing RGCs through cell transplants, but this process is still in the research and development stage and fraught with limitations that highlight the need for a more precise way to effectively repopulate these cells in 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 strategy for glaucoma cell replacement therapy.
In their new study, the researchers changed the microenvironment in the eye in a way that allowed them to take stem cells from the blood and turn them into retinal ganglion cells that were able to migrate and survive in the retina of the eye. They conducted their study in the retina of an adult mouse, but the implications of the work could one day be applied to the human retina, according to researchers who published their findings Nov. 6 in Proceedings of the National Academy of Sciences.
A limitation that hinders the success of current stem cell transplantation strategies in retinal studies is that the majority of donor cells remain at the injection site and do not migrate to where they are most needed. To identify an improved solution, the researchers created RGCs from stem cells and then tested the ability of various signaling molecules known as chemokines to guide these new neurons to their correct locations within the retina. The research team used a “big data” approach and screened hundreds of such molecules and receptors to find 12 unique to RGCs. They found that stroma-derived factor 1 was the best-performing molecule for both migration and engraftment.
“This method of using chemokines to guide the movement and integration of donor cells represents a promising approach to restore vision in glaucoma patients,” said senior author Petr Baranov, MD, PhD, of Mass Eye and Ear , who is also an assistant professor of ophthalmology at Harvard Medical School. “It has been an exciting journey to work with a team of talented scientists with unique expertise to develop new techniques in this study to modify the local environment to guide cellular behavior — techniques that may be applied to the treatment of other neurodegenerative conditions.” .
The study was done jointly by members of Baranov’s lab at Mass Eye and Ear, including industrialist and lead study author Jonathan R Soucy, PhD, and lead bioinformatician Emil Kriukov, MD.
In addition to Baranov, Soucy and Kriukov, study co-authors include Levi Todd, Monichan Phay, Volha V. Malechka, John Dayron Rivera and Thomas A Reh.
The study was funded by several grants from the National Eye Institute (NEI) of 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 discloses a patent incorporating the endogenous reprogramming technology described in this report with inventors LT and TAR.