Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic retinopathy

SA Mills; AI Jobling; MA Dixon; BV Bui; KA Vessey; JA Phipps; U Greferath; G Venables; VHY Wong; CHY Wong; Z He; F Hui; JC Young; J Tonc; E Ivanova; BT Sagdullaev; EL Fletcher

Journal article

Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic retinopathy

SA Mills, AI Jobling, MA Dixon, BV Bui, KA Vessey, JA Phipps, U Greferath, G Venables, VHY Wong, CHY Wong, Z He, F Hui, JC Young, J Tonc, E Ivanova, BT Sagdullaev, EL Fletcher

Proceedings of the National Academy of Sciences of the United States of America | NATL ACAD SCIENCES | Published : 2021

DOI: 10.1073/pnas.2112561118

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Abstract

Local blood flow control within the central nervous system (CNS) is critical to proper function and is dependent on coordination between neurons, glia, and blood vessels. Macroglia, such as astrocytes and Muller € cells, contribute to this neurovascular unit within the brain and retina, respectively. This study explored the role of microglia, the innate immune cell of the CNS, in retinal vasoregulation, and highlights changes during early diabetes. Structurally, microglia were found to contact retinal capillaries and neuronal synapses. In the brain and retinal explants, the addition of fractalkine, the sole ligand for monocyte receptor Cx3cr1, resulted in capillary constriction at regions of..

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University of Melbourne Researchers

Andrew Jobling Author

Bang Bui Author

Kirstan Vessey Author

Una Greferath Author

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Grants

Awarded by National Health and Medical Research Council

Funding Acknowledgements

We thank Dr. Leonid Churilov for his assistance with statistical analysis; Dr. Christine Nguyen and Mr. Darren Zhao for their assistance with blood gas analysis; Ms. Satya Gunnam for her assistance with immunohistochemical staining and analysis; and the Biological Optical Microscopy and Melbourne Cytometry (MBC node) Platforms at the University of Melbourne. This work was supported by research grants from the National Health and Medical Research Council (APP-2000669, APP-1138509) and the Australian Research Council (DP160102642, DP200102001, FT130100338).