When the eye’s drainage system clogs, intraocular pressure (IOP) builds up and causes damage. The pressure can lead to glaucoma and vision loss. Researchers headed by a team at Duke University School of Medicine have now found that a specialized set of immune cells known as resident tissue macrophages (RTMs) act as the cleanup crew, pointing to a promising new target for therapies to prevent a major cause of blindness.
Through their study, the researchers tracked fluorescently tagged resident tissue macrophages in mouse eyes. When they selectively removed these cells, the eye’s drain, or outflow, became clogged, fluid built up, and eye pressure increased.
The discovery could lead to the development of future glaucoma treatments. The next step will be research to identify these resident macrophages in human eye tissue. “This research helps us understand the role of the immune system in regulating eye pressure,” said Katy Liu, MD, PhD, assistant professor in the department of ophthalmology at Duke University School of Medicine. “Our findings show that resident macrophages are essential for maintaining healthy eye pressure,” said Liu. “Disruption of this system may contribute directly to the development of glaucoma.”
Added W. Daniel Stamer, PhD, the Joseph A.C. Wadsworth Distinguished Professor of Ophthalmology, and co-vice chair for basic science research, “Now we have a specific target for developing new therapies that can normalize the eye pressure and stop vision loss, in contrast to current medications that do not target the source of disease.”
Liu is first author, and Stamer co-corresponding author of the researchers’ published paper in Immunity, titled “Resident tissue macrophages maintain intraocular pressure homeostasis.”
Glaucoma is the second leading cause of blindness worldwide, the authors wrote. And while there are effective treatments that work by lowering intraocular pressure, some patients continue to lose vision due to inadequate IOP control.
“Intraocular pressure is tightly regulated by the conventional outflow tissues, preventing ocular hypertension that leads to neurodegeneration of the optic nerve, or glaucoma,” the team continued. Macrophages live in the eye’s drainage tissues, but until now, the role of resident macrophages in controlling eye pressure hasn’t been well understood. “Although macrophages reside throughout the conventional outflow tract, their role in regulating intraocular pressure remains unknown.”
Moreover, they pointed out, the “… question of whether macrophages are long-lived resident tissue macrophages (RTMs) versus steady-state monocyte-derived macrophages in the conventional outflow tract is important because macrophages are phenotypically distinct based on ontogeny and tissue microenvironment, factors that dictate their function.”
The researchers’ tests in experimental mice have now demonstrated the importance of these RTMs in maintaining IOP. They showed that IOP increased significantly in eyes depleted of RTMs. Conversely, they showed that depletion of monocyte-derived macrophages did not affect outflow resistance or IOP in a steady-state setting.
“Using complementary mouse model systems to dissect their relative roles, we show that long-lived RTMs in the conventional outflow pathway are essential to maintain a healthy IOP, and that long-lived RTMs and monocyte-derived macrophages have differential effects on IOP regulation,” they stated. The findings that these two different macrophage populations may have different roles in IOP regulation in the healthy state “… affords the potential to therapeutically target specific macrophage subpopulations in the outflow tract to lower IOP.”
Liu said, “The only way we can treat glaucoma is by lowering the eye pressure, yet we still have patients who go blind despite current treatments. This research helps us understand the role of the immune system in regulating eye pressure. “Our findings show that resident macrophages are essential for maintaining healthy eye pressure. Disruption of this system may contribute directly to the development of glaucoma.”
“Now we have a specific target for developing new therapies that can normalize the eye pressure and stop vision loss, in contrast to current medications that do not target the source of disease,” said Stamer. The authors added, “Future studies are needed to investigate the roles of long-lived RTMs and monocyte-derived macrophages in the outflow tract in normal IOP homeostasis versus disease.”
The Duke Eye Center has a long history of breakthroughs in glaucoma. “This discovery is a major step forward in understanding how the immune system contributes to the regulation of eye pressure,” said Daniel Saban, PhD, co-corresponding author, the Joseph A.C. Wadsworth Distinguished Professor of Ophthalmology, and vice chair of research strategy in the department of ophthalmology. “This research builds on Duke’s strong history of turning laboratory findings into real treatments for patients.”
