Müller cells are a type of glial cell found in the retina. These cells have been something of an overlooked middle child of eye research for a long time, says Wilmer’s Malia Edwards, Ph.D., a recently appointed assistant professor who is exploring the glial cell’s role in perpetuating age-related macular degeneration (AMD), the leading cause of blindness in those 50 and older.

Müller cells were once thought to play only a structural support role in the eye — the glue that holds everything together, Edwards notes. But she has been investigating the tendency of the glia to migrate out of the retina to other areas of the eye.

“Müller cells, which are usually very linear, start to lose that linear shape in AMD and begin to extend and migrate out of the retina, making these unusual membranes on top of and below the retina,” Edwards explains. She believes that the mechanisms stimulating glial changes may also play a role in retinitis pigmentosa and diabetic retinopathy.

Those membranes have several consequences in both the wet and dry forms of AMD. In the wet form, Edwards has shown that the glia develop into a membrane atop the retina over the diseased area with choroidal neovascularization. Importantly, these membranes are not visible to clinicians. Interestingly, the glia also appear to express a protein, VEGF, that is blocked to treat wet AMD. Edwards theorizes that the glial cells, therefore, might bind the treatment before it has a chance to reach its target. This could contribute to differences in treatment efficacy between patients. Understanding how and why these membranes form could help improve treatment of wet AMD and, potentially, other conditions with similar membranes.

In dry AMD, Edwards has noted that the glia also appear to extend and migrate to form similar membranes on the underside of the retina, between the retina and the layer immediately behind the retina. Known as the choroid, this layer of tissue provides nutrients and oxygen to the outer retina.

That avenue of research has been perhaps Edwards’ most promising and a focus of much of her decadelong research partnership with her mentor-turned- collaborator Gerard Lutty, Ph.D., one of the world’s foremost experts on the study of the choroid.

“We basically split the eye in half. He takes the choroid, I take the retinas, and we are able to see how changes in the choroid and the retina affect one another,” Edwards explains.

“In their migration under the retina in dry AMD, the Müller cells are likely releasing chemicals that communicate with the choroid that prevent the blood vessels from growing and seems to make the choroidal blood vessels die,” Lutty says. “Regardless, it's a destructive process to the retina and choroid.” Stem cells offer a potentially sight-saving treatment option for dry AMD, but the Müller membranes may form a wall-like structure, potentially blocking stem cell transplants and drug therapies from reaching their intended targets, Edwards says.

The collaboration between Edwards and Lutty began in 2009, when Edwards joined Lutty’s lab as a postdoctoral researcher. As Edwards’ career ascended, she began to establish her own independent research and now has her own lab — right next to Lutty’s in the Robert H. and Clarice Smith Building at Wilmer. It’s a professional progression all mentors hope for, Lutty says. The collaboration remains as close as ever. “We share lab space. We share thought processes. We share tissue. And we are still working together as a wonderful team,” Lutty says.

Philanthropy has played a key role in their partnership. Lutty is the G. Edward and G. Britton Durell Professor of Ophthalmology, a professorship established and endowed by the Altsheler-Durell Foundation, a family foundation chaired by David Durell.

The Durells’ gift has allowed Edwards and Lutty to purchase camera equipment and tools for creating animal models that are not covered through their grants from the National Institutes of Health.

“The Durells have been exceedingly good to us, and their philanthropy has advanced our work,” Lutty says. “We are deeply grateful to them for their generosity and support through the years.”