ArticleProceedings of the National Academy of Sciences of the United States of America2021
Fractalkine-induced microglial vasoregulation occurs within the retina and is altered early in diabetic retinopathy.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 79 papers, 1 of them a synthesis that pooled it.
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Who cites it
79 citing papers in PubMed, 1 synthesis or guideline pooled it, 112 citations in OpenAlex.
- Effects of diabetes on microglial physiology: a systematic review of in vitro, preclinical and clinical studies.Journal of neuroinflammation · 2023Pooled it
- Clinical Implications of the Novel Genetic Polymorphism Associated With Retinal Vein Occlusion: The East Asian GWAS Survey in a Single-Center Taiwanese Cohort.Translational vision science & technology · 2026Article
- Hyperglycemia-Induced Microglial CTSS Disrupts Blood-Retinal Barrier Integrity via PAR2-Dependent Downregulation of Endothelial MFSD2A.CNS neuroscience & therapeutics · 2026Article
- Article
- Ythdf2 loss in microglia aggravates ischemic retinopathy by increasing microglia activation and microvascular anomalies.Journal of advanced research · 2026Article
- L-DOPA Promotes Post-Treatment Neurovascular and Synaptic Homeostasis in Early Diabetic Retinopathy.Investigative ophthalmology & visual science · 2026Article
- Diabetes May Modulate the Association Between Age and Optical Coherence Tomography Angiography Parameters: A Serial, Cross-Sectional Study.Journal of personalized medicine · 2026Article
- Microglial polarization in retinal neovascularization: Friend or foe?Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Vitreoretinal Myeloid Cell Heterogeneity: Diverse Roles in Homeostasis, Immune Surveillance, and Pathophysiology.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Sympathetic Stress and Sleep Loss in Diabetic Retinopathy: Links to Retinal Blood-Flow Control.Biomedicines · 2026Review
- L-DOPA treatment promotes sustained neurovascular and synaptic homeostasis in the diabetic retina.bioRxiv : the preprint server for biology · 2026Article
- Chronic dental lighting disrupts blood-retinal barrier homeostasis via vascular and inflammatory pathways.International journal of oral science · 2026Article
- Capillary-Associated Microglia in Neurovascular Coupling: Localization, Mechanisms, and Disease Implications.Journal of neuroinflammation · 2026Review
- Relationship Between the Degree of Diabetic Retinopathy and Serum Fractalkine (CX3CL1) in Patients with Type 2 Diabetes: A Single-Center Cross-Sectional Study.Medicina (Kaunas, Lithuania) · 2026Article
- Dual immune armies in glaucoma: microglia and monocyte-derived macrophages.Frontiers in immunology · 2026Review
- Nanoparticle-Mediated Lutein Delivery for Diabetic Retinopathy: From Blood-Retinal Barrier Crossing to Neurovascular Unit Protection.International journal of nanomedicine · 2026Review
- Microglia in retinal vascular diseases: inflammatory mechanism and therapeutic target.International journal of ophthalmology · 2026Review
- Review: The role of microglia in diabetic retinopathy and its potential as a therapeutic target.Molecular vision · 2026Review
- Hyperglycemia impairs microglia responding to retinal vasculopathy via enhanced norepinephrine-ADRB2 signaling.Journal of neuroinflammation · 2025Article
- Dynamic modulation of the blood-brain barrier in the healthy brain.Nature reviews. Neuroscience · 2025Review
19 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
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 Müller 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 microglial contact. This vascular regulation was dependent on microglial Cx3cr1 involvement, since genetic and pharmacological inhibition of Cx3cr1 abolished fractalkine-induced constriction. Analysis of the microglial transcriptome identified several vasoactive genes, including angiotensinogen, a constituent of the renin-angiotensin system (RAS). Subsequent functional analysis showed that RAS blockade via candesartan abolished microglial-induced capillary constriction. Microglial regulation was explored in a rat streptozotocin (STZ) model of diabetic retinopathy. Retinal blood flow was reduced after 4 wk due to reduced capillary diameter and this was coincident with increased microglial association. Functional assessment showed loss of microglial-capillary response in STZ-treated animals and transcriptome analysis showed evidence of RAS pathway dysregulation in microglia. While candesartan treatment reversed capillary constriction in STZ-treated animals, blood flow remained decreased likely due to dilation of larger vessels. This work shows microglia actively participate in the neurovascular unit, with aberrant microglial-vascular function possibly contributing to the early vascular compromise during diabetic retinopathy.
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