Researchers Identify Microglia as Key Responders in Retinal Injury

In most tissues of the body, neutrophils are the primary immune cells that respond quickly to infection or injury. However, researchers at the Flaum Eye Institute and the Del Monte Institute for Neuroscience at the University of Rochester have discovered that the retina behaves differently. When photoreceptor cells in the retina are damaged, it is microglia that take action while neutrophils, although nearby in the blood vessels, are not recruited to assist.

This unexpected finding highlights a critical distinction in the immune response of the retina compared to other parts of the body. According to Jesse Schallek, PhD, associate professor of Ophthalmology and senior author of the study published in eLife, "This finding has high implications for what happens to millions of Americans who suffer vision loss through loss of photoreceptors. This association between two key immune cell populations is essential knowledge as we build new therapies that must understand the nuance of immune cell interactions."

Advanced Imaging Reveals Selective Immune Activation

To investigate the retina’s response to photoreceptor damage, researchers used adaptive optics imaging, a high-resolution camera technology developed at the University of Rochester. This technology allows scientists to observe single neurons and immune cells inside the living eye.

In mice models with photoreceptor injury, both neutrophils and microglia were present in the retinal environment. However, the research revealed that only microglia responded to the damage. Neutrophils remained uninvolved, and there was no evidence that microglia attempted to recruit them.

Immune Cloaking May Protect the Retina

The lack of neutrophil response suggests that the retina may utilize a form of immune cloaking. This mechanism might prevent an excessive immune reaction that could harm the sensitive retinal tissue rather than support healing.

"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. "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."

Implications for Degenerative Retinal Diseases

Photoreceptor cells are essential for vision because they convert light into electrical and chemical signals that are interpreted by the brain. These cells are unique to the retina and are vulnerable to damage from conditions such as age-related macular degeneration, retinitis pigmentosa, and cone rod dystrophy. Currently, there is no cure for these diseases.

This research demonstrates the potential to visualize single immune and neuronal cells in real time as they respond to retinal injury. These insights may inform the development of new therapeutic strategies by offering a better understanding of immune behavior in the retina.

Reference:

Derek Power et al, Photoreceptor loss does not recruit neutrophils despite strong microglial activation, eLife (2025). DOI: 10.7554/eLife.98662.4