Research out of the Schepens Eye Research at the Massachusetts Eye and Ear (MEE), and published in Proceedings of the National Academy of Sciences of the United States of America (PNAS), has identified a potential targeted cell replacement therapy for glaucoma.
Give me some background.
With an estimated 3.5% of the global population (over the age of 40) diagnosed with glaucoma—and projections for that number to continue to grow from 76 million (in 2020) to 111.8 million by 2040—the need for a targeted therapy persists.
Thus, researchers concluded that retinal ganglion cells (RGCs)—which, when damaged, cause vision loss in glaucoma—are in need of a replacement therapy in order to restore sight in glaucoma patients.
So what’s the roadblock with this?
Per the study’s researchers, despite prior research on cell transplant therapy, “RGC replacement remains an unsolved challenge in regenerative ophthalmology.”
Case in point: Current stem cell transplantation methods within the retinal space have typically involved a situation where donor cells do not migrate to the retina, where vision restoration could be possible.
And the hypothesis for this research?
Investigators hypothesized that an early guided migration of RGCs could significantly improve the structural and functional integration (which was previously identified to be closely associated) of donor and newborn RGCs.
The goal: to develop a framework for identifying microenvironment cues in order to control a specific donor cell behavior by using RGCs in both a substrate and migration function.
Exactly how did they do this?
Investigators performed an in-silico analysis of developing human retina’s “single-cell transcriptome,” identifying six candidates to guide stem cell-derived or newborn neurons.
After examining hundreds of signaling molecules (called “chemokines”) and receptors and performing in-vivo assays, they identified stromal cell-derived factor-1 (SDF1) as the most potent chemokine for RGC recruitment (including migration and transplantation)
Then what?
The RGCs from mouse and human stem cells were tested for differentiation, after which the investigators intravitreally transplanted these stem cell-derived RGCs and intravitreally delivered the recombinant SDF1 protein to “establish a chemokine gradient across the retina.”
And they determined …
They found (or, rather, confirmed their hypothesis) that, by using a quantitative approach to cell transplantation, donor cell behavior was controllable.
Translation: the investigators were able to adjust the eye’s microenvironment in a manner that allowed them to take stem cells from blood and turn them into RGCs capable of migrating and, potentially, survive in the retina.
What’s the significance of this?
Per Mass Eye and Ear, though the study was conducted on the retina of adult mice, this new strategy has the potential to be applied to the human retina—a groundbreaking treatment for glaucoma cell replacement therapy.
And study author feedback?
Per senior study author Petr Baranov, MD, PhD, of MEE: ““This method of using chemokines to guide donor cell movement and integration represents a promising approach to restoring vision in glaucoma patients.”
Dr. Baranov added that these techniques also have the potential to be applied to treat other neurodegenerative conditions.