Retinal Defense: Immune Cells Bypass Injury

New research reveals surprising immune response in the eye

In a significant departure from how most tissues react to damage, the eye’s delicate retina employs a distinct immune strategy. Researchers have discovered that while the body typically rushes neutrophils to sites of injury, the retina calls upon its own specialized immune cells, microglia, leaving circulating neutrophils unrecruited.

Microglia Lead the Charge

When photoreceptor cells in the retina, crucial for converting light into vision, are damaged, the brain’s own immune cells, microglia, are the primary responders. This is a notable difference from other bodily tissues where neutrophils, a type of white blood cell, usually serve as the initial defenders. Even when neutrophils pass through nearby blood vessels, they are not drawn into the damaged retinal area.

This observation holds significant implications for understanding and treating vision loss. “This finding has high implications for what happens for millions of Americans who suffer vision loss through loss of photoreceptors,” stated Jesse Schallek, PhD, an associate professor of Ophthalmology and senior author of the study published in *eLife*. 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.

Adaptive Optics Uncovers Unique Immune Behavior

Utilizing advanced adaptive optics imaging, a technology developed at the University of Rochester capable of visualizing individual neurons and immune cells within a living eye, scientists examined mouse retinas exhibiting photoreceptor damage. Their findings confirmed that only microglia activated in response to the injury, without enlisting the aid of neutrophils.

Researchers theorize this immune behavior might act as a protective mechanism, preventing an overwhelming influx of immune cells that could potentially cause further harm to the sensitive retina. 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, explained 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.

Understanding Diseases of Vision Loss

Photoreceptor cells are unique to the retina and are vital for sight. Numerous conditions, including age-related macular degeneration and retinitis pigmentosa, lead to the damage and death of these cells, with no current cures. This research provides a clearer picture of cellular communication during retinal damage, crucial for developing future treatments.

Globally, over 300 million people live with vision impairment, with the leading causes often involving damage to retinal cells. Understanding how the eye’s immune system functions, or in this case, differs, is key to developing effective therapies for conditions like macular degeneration, which affects millions worldwide. According to the World Health Organization, uncorrected refractive errors and vision impairment due to cataracts and glaucoma are leading causes of vision loss.

Future Directions in Ocular Immunology

The study, spearheaded by first author Derek Power, a laboratory technician in the Schallek lab, alongside contributions from Justin Elstrott, PhD, of Genentech Inc., was supported by grants from the National Eye Institute, Research to Prevent Blindness, and the Dana Foundation.

The research offers a novel window into the dynamic interactions of immune cells within the retina following injury, paving the way for more targeted therapeutic interventions for a range of blinding eye diseases.