Our Immune System Can See

Scientists have known for many years that immune cells are in the retina and that their numbers increase in inherited retinal diseases. This increase is also observed in age-related macular degeneration (AMD) that affects millions of people in the U.S. alone.

A new finding from a research team led by Daniel Saban, PhD, associate professor of ophthalmology, suggests that immune cells that protect us from infection might also help us see, in a study published in the journal Immunity. This study reveals that the immune system is actually needed to help nerve cells in the retina respond appropriately for vision. The research also showed that these same exact immune cells, called microglia, also protect the retina in inherited diseases that cause blindness in mice. This study reveals that the immune system is actually needed to help nerve cells in the retina respond appropriately for vision.

This work may lead to a new understanding for the causes of vision loss in such inherited retinal diseases in patients, which affects several million worldwide. “Microglia are traditionally thought of in terms of protecting nerves from infection,” says Saban, senior author of the paper. “However, scientists are now appreciating that these immune cells also play key roles in supporting the function of nerves even when there is no infection present.”

The precise identity of these immune cells in the disease setting was unknown. Microglia are easily mistaken for another immune cell type that can come in from the blood, called monocytes. Also unclear in the field is whether these immune cells in retinal disease are part of a problem, or rather are perhaps acting in some protective manner against the disease. These questions are important as immune cells accumulate next the critical layer in disease, called the retinal pigmented epithelium. Deterioration of this layer is thought to be a major cause of vision loss in AMD. “Our study shows that microglia, not monocytes, accumulate next to the retinal pigmented epithelium in the diseases we tested in mice,” states one of the lead authors of this study, Chen Yu, PhD, postdoctoral associate in Saban’s lab. “In addition, we found that these microglia actually protect this layer.” Since scientists are focused on trying to find out why the retinal pigmented epithelium deteriorates in AMD and how it can be protected to halt disease, these new findings may offer clues to the field.

Daniel Saban, PhD Associate Professor of Ophthalmology

The next steps for Saban’s team is to understand exactly how microglia protect this layer in disease and whether this system can be hacked for therapeutic purposes in retinal degenerative diseases The research was supported in part by BrightFocus, National Eye Institute/National Institutes of Health, and Research to Prevent Blindness.

Application of single cell RNA sequencing to understand the role of immune cells in retinal degenerative disorders. Image depicts our work flow, including enrichment of immune cells, RNA sequencing at the single cell level, bioinformatic analysis to identify novel subtypes of immune cells, and validation in tissues. This work identified a unique microglial subtype that restricts the progression of retinal degeneration.