Q&A: Could this discovery lead to a cure for glaucoma?

Our methods of detection for glaucoma diagnosis have gotten better, so that’s always influencing the numbers. It has been, and will likely continue to be for the foreseeable future, one of the leading causes of blindness. In the world and in the U.S., it’s a significant healthcare burden, costing billions of dollars per year, and leading to an entire infrastructure for surgery and medications, all focused on trying to decrease or minimize loss of vision from glaucoma.

Q. Can you summarize your findings?

A. The big picture is that, in glaucoma, there’s a lack of fluid flow out of the eye, and since the fluid can’t exit, the intraocular pressure, or IOP, increases. Currently, methods to treat it don’t work very well. You have to either have invasive surgery or take daily eye drops, which have a lot of side effects and poor patient compliance. 

Evan Scott leads a UVA research lab focused on developing immunotherapies for cancer, allergy, infectious disease and autoimmune disorders. (Contributed photo)

So, my lab and our collaborators at Northwestern, Mark Johnson and Ben Thompson, have been studying a gene called “Prox1” that we found can decrease or increase IOP depending on if its expression level goes up or down, respectively. We developed a new type of particle that can selectively modify the cells that have this gene, which we can regulate in order to control the pressure. 

Since these particles are targeted only to those cells, they don’t accumulate anywhere else in the eye, which avoids side effects.

As a result, we now have a new chronic mouse model to help us study how changes in IOP lead to glaucoma pathology and test different ways to cure it. Our goal is to develop a treatment that requires a single injection to the eye that can achieve a permanent decrease in pressure. The therapy is at least five years away from human testing.

Q. Who did you collaborate with on the research?

A. Mark Johnson is a biomedical engineer at Northwestern University. He’s spent decades looking at how fluid flow changes in the eye. On this and previous projects, we worked together to make cell-softening nanotherapies that decrease cell stiffness in strategic locations in the eye, allowing fluid to more easily exit back into circulation, thus decreasing IOP. While our prior work used targeted drug delivery to achieve this, our new findings have switched our focus to gene therapy.

Ben Thompson at Northwestern’s Feinberg School of Medicine is an expert in vascular biology and mouse models of glaucoma. He was instrumental in identifying Prox1 as the gene target and helping us develop and validate these models. So, it’s really a powerful and highly collaborative three-person team. One person figured out the stiffness issue. One person has the mouse models. And our side was developing the nanotherapy to selectively modify cells to better understand the pathology and identify therapeutic targets. 

Q. What do you do at UVA?

A. I am a professor in the biomedical engineering department in the School of Medicine. I was recruited about two years ago to direct the Institute for Nanoscale Scientific and Technological Advanced Research on campus, where we focus on nano/biomaterials science, nanotherapy and immunotherapy. We also provide services across the country to design and fabricate custom nanomaterials and therapeutic formulations.

Q. What is nanotherapy?

A. Nanomaterials are tiny nanoscale particles about the size of viruses, and you can package drugs and therapeutics inside them to more efficiently deliver drugs to where they are most effective at treating a disease and at significantly lower doses. 

The nanomaterials we use are very safe and nontoxic. They’re made of a biodegradable polymer, so they safely break up and exit the body. There’s no infection happening. 

These nanotherapeutics are so useful because our immune system, and our cells in general, have evolved to interact with things at the nanoscale. The immune system is always looking for nanoscale particulates and foreign materials because it naturally wants to remove viruses and cellular debris that shouldn’t be there. So, if you put a drug inside, you can decrease toxicity and get it only to very specific cells. That’s what we did in this study to safely modulate pressure in the eye without impacting off-target cells and processes.