Immune cells enter the retina through the same mechanism they use to penetrate other tissues in the body, with the molecule PECAM playing a key role in the process. This is the conclusion reached by researchers at Northwestern University, whose findings were published in The American Journal of Pathology.
The scientists studied the mechanism of transendothelial migration — the process by which leukocytes leave blood vessels and move into tissues in response to inflammation. Of particular interest were the blood vessels of the retina, which form part of the blood-retinal barrier that protects the eye from exposure to many substances and blood cells.
The study showed that leukocytes cross this barrier using the same mechanism as they do in other blood vessels throughout the body. The key “checkpoint” was found to be PECAM, or platelet and endothelial cell adhesion molecule, which is involved in the movement of leukocytes across blood vessel walls.
To track the development of inflammation, the researchers induced acute uveitis — inflammation of the uvea, the vascular layer of the eye — in mice. During the first few hours, neutrophils were the main immune cells entering the retina. They subsequently helped attract a second wave of immune cells, monocytes. After 48 hours, neutrophils had almost completely disappeared from the retina, while monocytes had transformed into macrophages and remained in the tissue for at least 72 hours.
At the same time, artificially removing neutrophils from the blood unexpectedly led to an increase in the number of monocytes entering the retina. According to the researchers, this may be because neutrophils release substances that help resolve the inflammatory response and promote tissue repair. Thus, they may not only initiate the immune response but also help limit it.
The scientists also investigated what would happen if PECAM were blocked using a monoclonal antibody. As a result, the number of neutrophils, T lymphocytes and monocytes entering the retina decreased significantly. Unlike complete neutrophil depletion, however, blocking PECAM helped control the migration of immune cells and improved the condition of animals with uveitis.
Uveitis is diagnosed in approximately 19 out of every 100,000 people in the United States each year. In resource-limited countries, infectious diseases may account for 30–60% of cases. Current treatment includes corticosteroids and broad-spectrum anti-infective drugs, but these therapies can cause side effects and systemic complications. According to the study authors, understanding the mechanisms that allow immune cells to enter the retina could help researchers develop more targeted treatments for inflammatory eye diseases.
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