Retinal immune cells may be key to preventing diabetes-related vision loss

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The findings could lead to new treatments that can be used at an early stage of the disease, long before any vision loss occurs.

New research could form the basis for the development of life-changing therapies that limit the impact of diabetic eye disease – a disease that could potentially affect some 1.7 million Australians with type 1 and type 2 diabetes .

Posted in PNASresearch from the University of Melbourne reveals how retinal immune cells change during diabetes, which may lead to new treatments that can be used at an early stage of the disease, long before any vision loss occurs.

“Until recently, immune cells in the nervous system were thought to remain silent, responding only to injury or illness. Our discovery expands our knowledge of what these cells do and shows a very unusual mechanism by which blood vessels are regulated. This is the first time that immune cells have been involved in the control of blood vessels and blood flow,” said co-author Professor Erica Fletcher.

According to Diabetes Australia, almost all people with type 1 diabetes and more than 60% of people with type 2 diabetes will develop some form of diabetic eye disease within 20 years of diagnosis. With 280 more people developing the disease every day, this breakthrough has important implications.

The research team discovered that a specific type of immune cell, called microglia, comes into contact with blood vessels and neurons in the retina and is able to alter blood flow to meet the neurons’ needs.

Professor Fletcher and co-author Dr Andrew Jobling identified the chemical signal by which immune cells communicate with blood vessels and demonstrated that immune cell regulation of blood vessels is abnormal in diabetes – a known disease to affect the blood vessels in the eye. The studies used preclinical animal models and a range of imaging methods that allowed researchers to see retinal immune cells in a live eye.

“We also isolated retinal immune cells from groups of normal and diabetic animals and analyzed their genome to identify how these cells communicate with blood vessels. Finally, we used a range of pharmacological tools to examine how blood vessels change in response to retinal immune cell activation,” said Dr. Jobling.

Professor Fletcher said the results highlight a new way to control and potentially prevent retinal changes in diabetes.

“This finding also has implications for our understanding of other retinal and brain diseases. Although at an early stage, these results suggest a new way of understanding vascular diseases of the brain with implications for our knowledge of stroke and Alzheimer’s disease,” Professor Fletcher said.

Importantly, they were able to show that at an early stage of diabetes – before there are any visible changes to the back of the eye – the blood vessels are abnormally narrow, affecting the way they supply the retinal neurons. Retinal immune cells have been implicated in this early vascular abnormality, implicating them as a new therapeutic target to control early retinal changes in diabetes.

It is hoped that the results will help develop new therapies to reduce the effects of vascular conditions in the retina and brain. These conditions include diabetes, Alzheimer’s disease, and vascular conditions such as stroke or retinal vascular occlusion.

Reference: “Fractalkine-induced microglial vasoregulation occurs in the retina and is impaired in early diabetic retinopathy” by Samuel A. Mills, Andrew I. Jobling, Michael A. Dixon, Bang V. Bui, Kirstan A. Vessey , Joanna A. Phipps , Ursula Greferath, Gene Venables, Vickie HY Wong, Connie HY Wong, Zheng He, Flora Hui, James C. Young, Josh Tonc, Elena Ivanova, Botir T. Sagdullaev and Erica L. Fletcher, December 13, 2021 , Proceedings of the National Academy of Sciences.
DOI: 10.1073/pnas.2112561118

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