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Photopic light-mediated down-regulation of local α(1A)-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis

We have reported the gateway reflex, which describes specific neural activations that regulate immune cell gateways at specific blood vessels in the central nervous system (CNS). Four types of gateway reflexes exist, all of which induce alterations in endothelial cells at specific vessels of the blo...

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Autores principales: Stofkova, Andrea, Kamimura, Daisuke, Ohki, Takuto, Ota, Mitsutoshi, Arima, Yasunobu, Murakami, Masaaki
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382936/
https://www.ncbi.nlm.nih.gov/pubmed/30787395
http://dx.doi.org/10.1038/s41598-019-38895-y
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author Stofkova, Andrea
Kamimura, Daisuke
Ohki, Takuto
Ota, Mitsutoshi
Arima, Yasunobu
Murakami, Masaaki
author_facet Stofkova, Andrea
Kamimura, Daisuke
Ohki, Takuto
Ota, Mitsutoshi
Arima, Yasunobu
Murakami, Masaaki
author_sort Stofkova, Andrea
collection PubMed
description We have reported the gateway reflex, which describes specific neural activations that regulate immune cell gateways at specific blood vessels in the central nervous system (CNS). Four types of gateway reflexes exist, all of which induce alterations in endothelial cells at specific vessels of the blood-brain barrier followed by inflammation in the CNS in the presence of CNS-autoreactive T cells. Here we report a new gateway reflex that suppresses the development of retinal inflammation by using an autoreactive T cell-mediated ocular inflammation model. Exposure to photopic light down-regulated the adrenoceptor pathway to attenuate ocular inflammation by suppressing breaching of the blood-retina barrier. Mechanistic analysis showed that exposure to photopic light down-regulates the expression of α(1A)-adrenoceptor (α(1A)AR) due to high levels of norepinephrine and epinephrine, subsequently suppressing inflammation. Surgical ablation of the superior cervical ganglion (SCG) did not negate the protective effect of photopic light, suggesting the involvement of retinal noradrenergic neurons rather than sympathetic neurons from the SCG. Blockade of α(1A)AR signaling under mesopic light recapitulated the protective effect of photopic light. Thus, targeting regional adrenoceptor signaling might represent a novel therapeutic strategy for autoimmune diseases including those that affect organs separated by barriers such as the CNS and eyes.
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spelling pubmed-63829362019-02-25 Photopic light-mediated down-regulation of local α(1A)-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis Stofkova, Andrea Kamimura, Daisuke Ohki, Takuto Ota, Mitsutoshi Arima, Yasunobu Murakami, Masaaki Sci Rep Article We have reported the gateway reflex, which describes specific neural activations that regulate immune cell gateways at specific blood vessels in the central nervous system (CNS). Four types of gateway reflexes exist, all of which induce alterations in endothelial cells at specific vessels of the blood-brain barrier followed by inflammation in the CNS in the presence of CNS-autoreactive T cells. Here we report a new gateway reflex that suppresses the development of retinal inflammation by using an autoreactive T cell-mediated ocular inflammation model. Exposure to photopic light down-regulated the adrenoceptor pathway to attenuate ocular inflammation by suppressing breaching of the blood-retina barrier. Mechanistic analysis showed that exposure to photopic light down-regulates the expression of α(1A)-adrenoceptor (α(1A)AR) due to high levels of norepinephrine and epinephrine, subsequently suppressing inflammation. Surgical ablation of the superior cervical ganglion (SCG) did not negate the protective effect of photopic light, suggesting the involvement of retinal noradrenergic neurons rather than sympathetic neurons from the SCG. Blockade of α(1A)AR signaling under mesopic light recapitulated the protective effect of photopic light. Thus, targeting regional adrenoceptor signaling might represent a novel therapeutic strategy for autoimmune diseases including those that affect organs separated by barriers such as the CNS and eyes. Nature Publishing Group UK 2019-02-20 /pmc/articles/PMC6382936/ /pubmed/30787395 http://dx.doi.org/10.1038/s41598-019-38895-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Stofkova, Andrea
Kamimura, Daisuke
Ohki, Takuto
Ota, Mitsutoshi
Arima, Yasunobu
Murakami, Masaaki
Photopic light-mediated down-regulation of local α(1A)-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
title Photopic light-mediated down-regulation of local α(1A)-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
title_full Photopic light-mediated down-regulation of local α(1A)-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
title_fullStr Photopic light-mediated down-regulation of local α(1A)-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
title_full_unstemmed Photopic light-mediated down-regulation of local α(1A)-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
title_short Photopic light-mediated down-regulation of local α(1A)-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
title_sort photopic light-mediated down-regulation of local α(1a)-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6382936/
https://www.ncbi.nlm.nih.gov/pubmed/30787395
http://dx.doi.org/10.1038/s41598-019-38895-y
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