What is it about?

Blood flow has to be tightly coupled to the metabolic requirements of the tissue. This study looked at how blood vessels in the back of the eye are regulated. We found that immune cells, called microglia, contact both blood vessels and neurons in the retina and are able to change blood flow to meet the needs of neurons. We identified the chemical signal by which immune cells communicate with blood vessels, and also demonstrated that immune cell regulation of blood vessels is abnormal in diabetes, a disease known to affect the blood vessels in the eye. Importantly, we found that at a very early stage of diabetes, before there are any visible changes at the back of the eye, blood vessels are abnormally narrow, affecting the way they supply the neurons of the retina. Retinal immune cells were implicated in this early vascular abnormality, implicating them as a novel therapeutic target for controlling early changes in the retina in diabetes. These are highly novel findings, that expand what we know about immune cells in the retina and brain. Up until only recently, immune cells of the nervous system were thought to sit quietly, only responding when injury or disease occurred. Our finding expands our knowledge of what these cells do and shows a highly unusual mechanism by which blood vessels are regulated. This is the first time, immune cells have been implicated in controlling blood vessel and blood flow. In the nervous system, vascular regulation has been attributed to a support cell called an astrocyte. Our results suggest that vascular regulation is more complex than previously thought.

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Why is it important?

The major implication of these findings is in understanding the mechanism(s) by which vascular function is abnormal at an early stage of diabetes. Diabetes is one of the leading causes of irreversible vision loss especially in those of working age. We know that diabetes can affect all cells in the retina. These results suggest that there are vascular deficits from a very early stage of diabetes that are caused by anomalies in immune cells. In the longer term, understanding how retinal immune cells change during diabetes may lead to new treatments that can be used from an early stage of disease, well before any loss of vision.


Undertaking this project has been a highly rewarding but challenging task and has involved a number of people from across a range of academic institutions. Our results have uncovered a novel role of microglia that I believe is going to be very important for our understanding of vascular disease. I hope you find this article interesting and thought provoking.

Professor Erica Fletcher
University of Melbourne

Read the Original

This page is a summary of: Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic retinopathy, Proceedings of the National Academy of Sciences, December 2021, Proceedings of the National Academy of Sciences,
DOI: 10.1073/pnas.2112561118.
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