ARVO 2023: Retinal Engineering and RGC Replacement

Thomas V. Johnson, MD, PhD, sat down with David Hutton, Managing Editor, Ophthalmology Times®, to discuss his presentation at this year's ARVO meeting on retinal engineering and RGC replacement.

Video transcript

Editor’s note: This transcript has been edited for clarity.

David Hutton:

I'm David Hutton of Ophthalmology Times. The Association for Research in Vision and Ophthalmology is holding its annual conference in New Orleans this year. I'm joined today by Dr. Thomas Johnson, who presented "Retinal Engineering and RGC Replacement: Enhancing Integration of Transplanted RGCs." Thank you so much for joining us today. Tell us about your presentation.

Thomas V. Johnson, MD, PhD:

Well, our lab's work is focused on developing new therapies that have the potential to restore vision for patients with optic neuropathys, including glaucoma.

Currently, all treatments we have available can slow or halt disease worsening, but don't restore vision that's already been lost. Now in order to do this, we think that replacing the types of nerve cells that die in glaucoma and other optic neuropathys within the visual pathway may be able to lead to vision restoration. The types of cells that we're talking about here are retinal ganglion cells, or RGCs.

So our lab's work focuses on differentiating or creating RGCs from human stem cells, and figuring out how we can transplant those into the eyes of animal models of optic neuropathy and get those cells to integrate into the visual pathway.

Our initial work showed that if we transplant RGCs, into the eyes of mice, and don't do anything else, spontaneously, they'll survive inside the eye. But they really don't do a good job of engrafting into the retina. They sit on, and adhere to the surface of the retina, but they don't send any dendrites or neurite processes into the tissue. Which is important because that's how they're going to communicate with the retina and receive signals about the light entering the eye, so that they can eventually communicate that information to the brain.

So the work that we've done over the past couple of years has identified an important obstacle to the integration of these cells. And that obstacle is the internal limiting membrane [ILM] of the retina. That's a basement membrane that sits on the surface of the retina, and divides the retina from the vitreous cavity right above it.

Our work suggests that retinal ganglion cells, when they encounter the ILM, seem to view it sort of as a growth substrate and a barrier that they can grow on but not through. So we've developed a couple of different methodologies to permeabilized, or make pores, in the ILM. And found that if we transplant RGCs, in that context, they begin to actually migrate through the ILM and engraft into the retina. Where they can elaborate dendrites in the inner plexiform layer, and begin to make synapses with the host retinal cells, the bipolar cells and emigrant cells, so that they can then receive information about vision and eventually communicate that to the brain.

David Hutton:

Ultimately, what can this mean for patients?

Thomas V. Johnson, MD, PhD:

Well, this is one step in a series of obstacles and challenges that have to be overcome in order to figure out how we might one day transplant stem cell derived RGCs into the eyes of patients.

Ultimately, we need them to not only incorporate into the retina and create synapses with the recipient's retinal cells, we need them to also grow a long axon through the optic nerve and into the parts of the brain that receive visual information.

If we can do that, then that may be a means to create therapies and surgeries and transplants that patients could receive that might have the potential to actually bring back vision that's been lost from glaucoma and other optic neuropathies.