Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

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Abstract

Microglia are the primary resident retinal macrophages that monitor neuronal activity in real-time and facilitate angiogenesis during retinal development. In certain retinal diseases, the activated microglia promote retinal angiogenesis in hypoxia stress through neurovascular coupling and guide neovascularization to avascular areas (e.g., the outer nuclear layer and macula lutea). Furthermore, continuously activated microglia secrete inflammatory factors and expedite the loss of the blood-retinal barrier which causes irreversible damage to the secondary death of neurons. In this review, we support microglia can be a potential cellular therapeutic target in retinopathy. We briefly describe the relevance of microglia to the retinal vasculature and blood-retinal barrier. Then we discuss the signaling pathway related to how microglia move to their destinations and regulate vascular regeneration. We summarize the properties of microglia in different retinal disease models and propose that reducing the number of pro-inflammatory microglial death and conversing microglial phenotypes from pro-inflammatory to anti-inflammatory are feasible for treating retinal neovascularization and the damaged blood-retinal barrier (BRB). Finally, we suppose that the unique properties of microglia may aid in the vascularization of retinal organoids.

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Fate mapping analysis reveals that adult microglia derive from primitive macrophages.

Florent Ginhoux, Melanie Greter, Marylène Leboeuf … (2010)

Microglia are the resident macrophages of the central nervous system and are associated with the pathogenesis of many neurodegenerative and brain inflammatory diseases; however, the origin of adult microglia remains controversial. We show that postnatal hematopoietic progenitors do not significantly contribute to microglia homeostasis in the adult brain. In contrast to many macrophage populations, we show that microglia develop in mice that lack colony stimulating factor-1 (CSF-1) but are absent in CSF-1 receptor-deficient mice. In vivo lineage tracing studies established that adult microglia derive from primitive myeloid progenitors that arise before embryonic day 8. These results identify microglia as an ontogenically distinct population in the mononuclear phagocyte system and have implications for the use of embryonically derived microglial progenitors for the treatment of various brain disorders.

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The Microglial Sensome Revealed by Direct RNA Sequencing

Suzanne E Hickman, Nathan D. Kingery, Toshiro K Ohsumi … (2013)

Microglia, the principal neuroimmune sentinels of the brain, continuously sense changes in their environment and respond to invading pathogens, toxins and cellular debris. Microglia exhibit plasticity and can assume neurotoxic or neuroprotective priming states that determine their responses to danger. We used direct RNA sequencing, without amplification or cDNA synthesis, to determine the quantitative transcriptomes of microglia of healthy adult and aged mice. We validated our findings by fluorescent dual in-situ hybridization, unbiased proteomic analysis and quantitative PCR. We report here that microglia have a distinct transcriptomic signature and express a unique cluster of transcripts encoding proteins for sensing endogenous ligands and microbes that we term the “sensome”. With aging, sensome transcripts for endogenous ligand recognition are downregulated, whereas those involved in microbe recognition and host defense are upregulated. In addition, aging is associated with an overall increase in expression of microglial genes involved in neuroprotection.

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Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor.

Christopher N. Parkhurst, Guang. Yang, Ipe Ninan … (2013)

Microglia are the resident macrophages of the CNS, and their functions have been extensively studied in various brain pathologies. The physiological roles of microglia in brain plasticity and function, however, remain unclear. To address this question, we generated CX3CR1(CreER) mice expressing tamoxifen-inducible Cre recombinase that allow for specific manipulation of gene function in microglia. Using CX3CR1(CreER) to drive diphtheria toxin receptor expression in microglia, we found that microglia could be specifically depleted from the brain upon diphtheria toxin administration. Mice depleted of microglia showed deficits in multiple learning tasks and a significant reduction in motor-learning-dependent synapse formation. Furthermore, Cre-dependent removal of brain-derived neurotrophic factor (BDNF) from microglia largely recapitulated the effects of microglia depletion. Microglial BDNF increases neuronal tropomyosin-related kinase receptor B phosphorylation, a key mediator of synaptic plasticity. Together, our findings reveal that microglia serve important physiological functions in learning and memory by promoting learning-related synapse formation through BDNF signaling. Copyright © 2013 Elsevier Inc. All rights reserved.

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Author and article information

Contributors

Kai Yao: URI : https://loop.frontiersin.org/people/1391301/overview

Journal

Journal ID (nlm-ta): Front Mol Neurosci

Journal ID (iso-abbrev): Front Mol Neurosci

Journal ID (publisher-id): Front. Mol. Neurosci.

Title: Frontiers in Molecular Neuroscience

Publisher: Frontiers Media S.A.

ISSN (Electronic): 1662-5099

Publication date (Electronic): 23 January 2023

Publication date Collection: 2023

Volume: 16

Electronic Location Identifier: 1100254

Affiliations

[1] ¹Institute of Visual Neuroscience and Stem Cell Engineering, Wuhan University of Science and Technology , Wuhan, China

[2] ²College of Life Sciences and Health, Wuhan University of Science and Technology , Wuhan, China

[3] ³Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan University of Science and Technology , Wuhan, China

Author notes

Edited by: Ashley S. Harms, University of Alabama at Birmingham, United States

Reviewed by: Francesca Massenzio, Università di Bologna, Italy; Mirko H. H. Schmidt, Dresden University of Technology, Germany

*Correspondence: Kai Yao, kyao21@ 123456outlook.com

^†These authors have contributed equally to this work

This article was submitted to Molecular Signalling and Pathways, a section of the journal Frontiers in Molecular Neuroscience

Article

DOI: 10.3389/fnmol.2023.1100254

PMC ID: 9899825

PubMed ID: 36756614

SO-VID: 31df214a-7888-4fa9-9852-69c505eb2e88

License:

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

History

Date received : 16 November 2022

Date accepted : 03 January 2023

Page count

Figures: 5, Tables: 1, Equations: 0, References: 227, Pages: 21, Words: 18487

Funding

Funded by: National Natural Science Foundation of China, doi 10.13039/501100001809;

Microglia: The breakthrough to treat neovascularization and repair blood-retinal barrier in retinopathy

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Most cited references 227

Fate mapping analysis reveals that adult microglia derive from primitive macrophages.

The Microglial Sensome Revealed by Direct RNA Sequencing

Microglia promote learning-dependent synapse formation through brain-derived neurotrophic factor.

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