Macrophages Help Maintain Eye Pressure with Implications for Glaucoma

Eyes are the windows to the world, but vision can decline with age or other factors. Impairment of the eye’s drainage system can lead to elevated intraocular pressure (IOP). Over time, increased IOP may damage the optic nerve, potentially causing glaucoma and vision loss.

Immune cells in the tissues that regulate IOP are recognized as important players; however, their contribution to maintaining eye pressure is not fully understood. To address this question, Katy Liu, a clinician-scientist in ophthalmology at Duke University School of Medicine, and her colleagues investigated the abundant population of macrophages present in eye tissue.

Their findings, published in Immunity, revealed that long-lived resident tissue macrophages in the eye maintain IOP.¹ When these cells were absent in an animal model, the eye’s drainage system became clogged, fluid accumulated, and eye pressure increased. “This research helps us understand the role of the immune system in regulating eye pressure,” Liu said in a press release. The findings highlight the importance of resident macrophages in eye health and suggest they could be a promising target for therapies aimed at preventing a major cause of blindness.

The eye constantly produces aqueous humor, which is the fluid found inside the front part of the eye, to maintain eye pressure and provide nutrients for the lens and cornea. It must also drain from the eye through a specialized outflow pathway to keep IOP at a healthy range. This fluid first passes through the trabecular meshwork (TM), through Schlemm’s canal (SC), and then through the distal vessels into the bloodstream. To investigate the role of macrophages in this tissue microenvironment, the researchers fluorescently tagged them in mouse eyes.

They observed a high abundance of long-lived resident tissue macrophages (RTMs) within the TM, whereas more distal regions of the fluid outflow pathway contained mainly steady-state monocyte-derived macrophages that are continuously replenished. To evaluate the functions of these two macrophage populations, the researchers selectively depleted each group.

Mice lacking RTMs showed reduced aqueous humor outflow compared to control mice. Because much of the outflow resistance is generated in the proximal regions of the drainage pathway—particularly the TM and SC—these findings suggest that RTMs play an important role in maintaining IOP homeostasis. In contrast, the depletion of monocyte-derived macrophages did not produce a significant effect on the mice’s eyes compared with control mice.

Then, the researchers further examined whether the macrophages contribute to extracellular matrix (ECM) turnover, a process that is dysregulated in glaucoma. Here, they observed a similar pattern between the two macrophage populations. When they selectively depleted RTMs, the outflow tract tissue exhibited significantly greater cell membrane deposits, indicating impaired ECM turnover. Depletion of the monocyte-derived macrophages did not produce differences compared with controls.

These findings highlight the role of the immune system in IOP homeostasis. The researchers acknowledge that further research is needed to elucidate the roles of these macrophages in a healthy versus disease state; however, the findings may lead to the development of future glaucoma treatments.