Researcher Q&A: Growing Cells for Glaucoma
BrightFocus Editor, Science Communications
Jason Meyer, PhD, a National Glaucoma Research grantee, is investigating new cellular approaches for the study of glaucoma.
My groups research focuses exactly on trying to develop new cellular approaches for the study of glaucoma.
To do this, we use what are known as induced pluripotent stem cells or iPS cells for short, and what these iPS cells are, are a type of stem cell that could become any cell type of the body. And one of the powerful thing powerful things about this is that these iPS cells start off as a cell from our body, usually like a skin cell or a blood cell that is then genetically reprogrammed to become a stem cell.
When these cells are donated by someone with a particular disease, such as glaucoma, especially when there is a genetic basis for this disease, now, these cells are intrinsically programmed. They have the blueprints inside their DNA to develop some features of that disease. So when we turn these donated cells into stem cells, they could be they become a very powerful model for us to study some of the pathways that are going wrong in the disease, now using cells in the dish.
They already have those blueprints that develop the disease, this obviously wouldn't be the best scenario to use these to try to replace the cells that have been lost because they could possibly suffer the same fate because they have that same genetic predisposition. So this is an area of ongoing research, and also speaks to one of the other areas of research in my lab where we use a tool that's called CRISPR gene editing. And what CRISPR gene editing does is that it allows us to introduce small changes into the DNA of the cells. So, if there is a genetic predisposition to the disease that we know of already, we can use these gene editing technologies to then correct that gene mutation.
Jason Meyer, PhD, is a BrightFocus Foundation success story and a pioneer in the effort to regenerate eye tissue that is damaged by glaucoma. It’s something the eye cannot do on its own, and it will help solve one of the greatest challenges ever attempted in vision science: that of replacing lost sight.
Dr. Meyer received early grants from the BrightFocus National Glaucoma Research (NGR) program to develop research expertise in this area. He’s now an associate professor of Medical and Molecular Genetics at Indiana University School of Medicine, and part of its Stark Neurosciences Research Institute.
Last year, Dr. Meyer and four other current and former BrightFocus grantees at separate institutions were awarded $6.7 million in funding over five years from the National Eye Institute. Their goal: to collaborate on ways to improve the long-term survival and integration of transplanted retinal cells that are destroyed in glaucoma. [He’s also a 2022-24 NGR grantee with a project to develop stem cell modeling of glaucoma in African descendants having a high-risk genetic variant of the disease.]
In this Q&A, Dr. Meyer explains why it’s particularly difficult to regrow and restore function to eye tissue destroyed by glaucoma—and shares hope about the enormous progress being made.
You have been a leader in efforts to artificially grow cells for study and for the future aim of restoring vision lost to glaucoma. Can you tell us more?
My group focuses on trying to develop new cellular approaches for the study of glaucoma. To do this, we use what are known as induced pluripotent stem (iPS) cells. These cells start off as a cell from our body, usually a skin cell or blood cell, that is then genetically reprogrammed to become a stem cell.
When donated by someone with a particular disease, such as glaucoma, these cells have the blueprints inside their DNA to develop some features of that disease. When we turn these donated cells into stem cells, they become a very powerful model for us to study the disease in a dish. We look at the cells in close detail—long before a patient would develop symptoms— and ask, “What's leading to those early changes?”
Some work is focused on retinal ganglion cells, how they interact with other supporting cells in the nervous system, and how these interactions go wrong in glaucoma. We're hopefully getting towards a more holistic approach, [also] looking at how support from their neighbors may be modified that makes a condition even worse. This leads us to a more well-rounded approach to eventually developing treatments for glaucoma.
As we look ahead to one day treating glaucoma with adult stem cells, will those cells be reprogrammed not to have glaucoma?
This speaks to one of the other areas of research in my lab. CRISPR gene editing allows us to introduce small changes into the DNA of the cells to correct that gene mutation. So if these [iPS] cells will then be used for cellular therapy to repair the damaged retina, they will not have the underlying genetic mutation, and will hopefully be maintained as happy and healthy cells.
What are the special challenges of regenerating sight lost to glaucoma? Please tell us about the eye-brain connection, and why it's so difficult to restore.
The connection between the eye and the brain comes from a type of cell known as the retinal ganglion cell (RGC) that are damaged in glaucoma. Ordinarily, they would send out long branches called axons to connect the eye with the brain. This is the only connection between the eye and the brain, so in glaucoma, where these RGCs are damaged, you're essentially severing that connection between the eye and the brain, resulting in vision loss or perhaps blindness.
There are a number of challenges facing us before we can use stem cells to repair the retina and restore vision. One is being able to turn the stem cells into RGCs—and that we have actually become very good at. But one of the things that sets glaucoma apart—a considerable and exciting challenge—is to restore these [eye-brain] connections.
If you think of nerve cells like wires in electronic device, these wires need to have the right connections so they link up in the circuit of our brain. Retinal ganglion cells are also what are known as projection neurons, so these connections have to occur over long distances. There's a lot that we need to still understand about how these cells make connections. But we're encouraged by all the fantastic research that's being done, including by other BrightFocus-sponsored researchers making great progress towards this.
Please say more about how you’re part of a “dream team” of current and former BrightFocus NGR grantees who received major funding from the National Eye Institute last year to work together on this effort.
Some scientific questions are very complex, and no one can have all the expertise at their disposal; this requires us to develop strong collaborations. My group is working with other current or former BrightFocus-funded researchers. We all have our own distinct set of expertise and skills that are complimentary to each other. And when we have that combined expertise, we create a powerful team that can really, we hope, address some of the challenges of using stem cells to repair the damaged retina in glaucoma.
Ultimately, what do you hope your research is able to achieve?
We hope that by developing these stem cell models, either to repair the damaged retina, or as a tool where we can study what's going wrong, we’ll add a powerful tool for the scientific community. We can now start addressing some of these problems, not just by one approach, but by multiple approaches, and hopefully get to therapeutics or cures for these diseases a lot faster.
What developments in glaucoma research are you most excited about?
There are a lot of things that are exciting. The ability to regrow RGCs is exciting. Trying to restore these connections with the nervous system is exciting.
What I'm also excited about is tackling the issue of neuroinflammation. This takes a more holistic approach of looking not only at RGCs, the primary cell type that's affected in glaucoma, but also damage to supporting cells that is compounding the problems of the RGCs. By taking this “big picture” approach to neuroinflammation, I think we're really going to make significant advances a lot faster.
That’s good to hear! Finally—has BrightFocus funding been of help to you along the way?
BrightFocus funding has been invaluable at multiple stages of my career. BrightFocus provided me with my very first research grant, when I was a brand-new investigator, and that helped launch my career. More recently, it has helped me to advance my lab’s research in new directions that are promising, but still kind of preliminary. It’s helped us launch in new directions and grow our research.
I know I speak not just for myself, but for many other investigators who have had similar starts, that BrightFocus has become a fantastic foundation to provide support for researchers at varying stages of their career.
- Can Stem Cell Treatments Cure My Glaucoma? (Expert Article)
- Protecting and Regenerating the Optic Nerve
- “Dream Team” of BrightFocus Alums Receive Major NIH Vision Grant (Research News)
About BrightFocus Foundation
BrightFocus Foundation is a premier nonprofit funder of research to defeat Alzheimer’s, macular degeneration, and glaucoma worldwide. Through its flagship research programs—Alzheimer’s Disease Research, National Glaucoma Research, and Macular Degeneration Research—the Foundation is currently supporting a $75 million portfolio of 287 scientific projects worldwide. BrightFocus has awarded nearly $275 million in groundbreaking medical research funding since inception and shares the latest research findings, expert information, and bilingual disease resources to empower the millions impacted by these devasting diseases worldwide. Join our community at brightfocus.org.
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