Researcher Q&A: Growing Cells for Glaucoma

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.