Researchers examine brain immune cell impact on the eye

Assistant Professor of Ophthalmology Jesse Schallek, PhD, right, and lab manager Derek Power, MS, in their lab in the University of Rochester’s Flaum Eye Institute. Image credit: J. Adam Fenster / University of Rochester

A recent study evaluating the interaction between 2 classes of brain immune cells have uncovered unique ways that the retina responds to damage that set it apart from other tissues in the body.^1,2 Researchers from the Flaum Eye Institute and Del Monte Institute for Neuroscience at the University of Rochester found that when photoreceptor cells in the retina are damaged, the microglia and neutrophils react differently in that the microglia respond and the neutrophils are not recruited, even though they pass through nearby blood vessels, according to a news release.¹

“Using cutting-edge retinal imaging modalities, we find that resident microglia become locally activated and regionally responsive to focal laser lesion,” the study authors stated. “They migrate away from their stratified locations near plexiform layers of the retina and toward the site of damage within hours to weeks after injury. However, systemic neutrophils, which are typically regarded as first-line responders to tissue damage, are not recruited to this damage despite neutrophils flowing within tens of microns away from the location of damage.”

The study was published in eLife with Derek Power, MS, of the Center for Visual Science and Flaum Eye Institute at the University of Rochester as first author.²

“This finding has high implications for what happens for millions of Americans who suffer vision loss through loss of photoreceptors,” said Jesse Schallek, PhD, associate professor of Ophthalmology and senior author of the study, in the release. “This association between 2 key immune cell populations is essential knowledge as we build new therapies that must understand the nuance of immune cell interactions.”

Researchers used adaptive optics scanning light ophthalmoscopy (AOSLO) to study retinas in mice with photoreceptor damage, specifically photoreceptor laser injury.² The camera images single neurons and immune cells inside the eye.¹ A day after injury, scanning light ophthalmoscopy “revealed bright, focal congregations of microglia at injury locations in contrast to undamaged locals, which maintained a distribution of lateral tiling,” according to study authors. However, at 1-, 3-, 7-day, and 2-month follow-up, researchers did not find evidence of neutrophil involvement, with “a notable lack of rolling/crawling neutrophils (or any putative leukocyte) in large arterioles or venules surrounding the injury.”²

“What is remarkable here is that the passing neutrophils are so close to the reactive microglia, and yet they do not signal to them to assist in damage recovery,” said Schallek in the release. “This is notably different than what is seen in other areas of the body where neutrophils are the first to respond to local damage and mount an early and robust response.”

While the study is “some of the earliest reports of single immune cell interactions in the living retina,” study authors noted limitations in its narrow exploration of 1 type of injury of the retina.² Including conditions of greater severity with increased power, duration, and extent of light damage, models of systemic and local infection, response to therapy that may modulate the immune response, and examining immune cell activity in models of retina disease were recommended for future studies.²

“Beyond the context of this specific finding, we share this work with the excitement that AOSLO cellular-level imaging may reveal the interaction of multiple immune cell types in the living retina,” the study authors concluded. “By using fluorophores associated with specific immune cell populations, the complex dynamics that orchestrate the immune response may be examined in this specialized tissue. This work and future studies may reveal further insights to the interactions of single immune cells in the living body in a noninvasive way.”

References:

1. Hayduk KS. Researchers find brain immune cells regulate vision health. University of Rochester Medical Center. July 24, 2025. Accessed August 19, 2025. https://www.urmc.rochester.edu/news/publications/neuroscience/researchers-find-brain-immune-cells-regulate-vision-health

2. Power D, Elstrott J, Schallek J. Photoreceptor loss does not recruit neutrophils despite strong microglial activation. eLife. 2025;13:RP98662. https://doi.org/10.7554/eLife.98662.4