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In vivo imaging reveals transient microglia recruitment and functional recovery of photoreceptor signaling after injury

Microglia respond to damage and microenvironmental changes within the central nervous system by morphologically transforming and migrating to the lesion, but the real-time behavior of populations of these resident immune cells and the neurons they support have seldom been observed simultaneously. He...

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Autores principales: Miller, Eric B., Zhang, Pengfei, Ching, Karli, Pugh, Edward N., Burns, Marie E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: National Academy of Sciences 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697899/
https://www.ncbi.nlm.nih.gov/pubmed/31350349
http://dx.doi.org/10.1073/pnas.1903336116
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author Miller, Eric B.
Zhang, Pengfei
Ching, Karli
Pugh, Edward N.
Burns, Marie E.
author_facet Miller, Eric B.
Zhang, Pengfei
Ching, Karli
Pugh, Edward N.
Burns, Marie E.
author_sort Miller, Eric B.
collection PubMed
description Microglia respond to damage and microenvironmental changes within the central nervous system by morphologically transforming and migrating to the lesion, but the real-time behavior of populations of these resident immune cells and the neurons they support have seldom been observed simultaneously. Here, we have used in vivo high-resolution optical coherence tomography (OCT) and scanning laser ophthalmoscopy with and without adaptive optics to quantify the 3D distribution and dynamics of microglia in the living retina before and after local damage to photoreceptors. Following photoreceptor injury, microglia migrated both laterally and vertically through the retina over many hours, forming a tight cluster within the area of visible damage that resolved over 2 wk. In vivo OCT optophysiological assessment revealed that the photoreceptors occupying the damaged region lost all light-driven signaling during the period of microglia recruitment. Remarkably, photoreceptors recovered function to near-baseline levels after the microglia had departed the injury locus. These results demonstrate the spatiotemporal dynamics of microglia engagement and restoration of neuronal function during tissue remodeling and highlight the need for mechanistic studies that consider the temporal and structural dynamics of neuron–microglia interactions in vivo.
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spelling pubmed-66978992019-08-19 In vivo imaging reveals transient microglia recruitment and functional recovery of photoreceptor signaling after injury Miller, Eric B. Zhang, Pengfei Ching, Karli Pugh, Edward N. Burns, Marie E. Proc Natl Acad Sci U S A PNAS Plus Microglia respond to damage and microenvironmental changes within the central nervous system by morphologically transforming and migrating to the lesion, but the real-time behavior of populations of these resident immune cells and the neurons they support have seldom been observed simultaneously. Here, we have used in vivo high-resolution optical coherence tomography (OCT) and scanning laser ophthalmoscopy with and without adaptive optics to quantify the 3D distribution and dynamics of microglia in the living retina before and after local damage to photoreceptors. Following photoreceptor injury, microglia migrated both laterally and vertically through the retina over many hours, forming a tight cluster within the area of visible damage that resolved over 2 wk. In vivo OCT optophysiological assessment revealed that the photoreceptors occupying the damaged region lost all light-driven signaling during the period of microglia recruitment. Remarkably, photoreceptors recovered function to near-baseline levels after the microglia had departed the injury locus. These results demonstrate the spatiotemporal dynamics of microglia engagement and restoration of neuronal function during tissue remodeling and highlight the need for mechanistic studies that consider the temporal and structural dynamics of neuron–microglia interactions in vivo. National Academy of Sciences 2019-08-13 2019-07-26 /pmc/articles/PMC6697899/ /pubmed/31350349 http://dx.doi.org/10.1073/pnas.1903336116 Text en Copyright © 2019 the Author(s). Published by PNAS. https://creativecommons.org/licenses/by-nc-nd/4.0/ https://creativecommons.org/licenses/by-nc-nd/4.0/This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND) (https://creativecommons.org/licenses/by-nc-nd/4.0/) .
spellingShingle PNAS Plus
Miller, Eric B.
Zhang, Pengfei
Ching, Karli
Pugh, Edward N.
Burns, Marie E.
In vivo imaging reveals transient microglia recruitment and functional recovery of photoreceptor signaling after injury
title In vivo imaging reveals transient microglia recruitment and functional recovery of photoreceptor signaling after injury
title_full In vivo imaging reveals transient microglia recruitment and functional recovery of photoreceptor signaling after injury
title_fullStr In vivo imaging reveals transient microglia recruitment and functional recovery of photoreceptor signaling after injury
title_full_unstemmed In vivo imaging reveals transient microglia recruitment and functional recovery of photoreceptor signaling after injury
title_short In vivo imaging reveals transient microglia recruitment and functional recovery of photoreceptor signaling after injury
title_sort in vivo imaging reveals transient microglia recruitment and functional recovery of photoreceptor signaling after injury
topic PNAS Plus
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6697899/
https://www.ncbi.nlm.nih.gov/pubmed/31350349
http://dx.doi.org/10.1073/pnas.1903336116
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