Photopic light-mediated down-regulation of local α1A-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F19%3A43917729" target="_blank" >RIV/00216208:11120/19:43917729 - isvavai.cz</a>
Result on the web
<a href="https://doi.org/10.1038/s41598-019-38895-y" target="_blank" >https://doi.org/10.1038/s41598-019-38895-y</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1038/s41598-019-38895-y" target="_blank" >10.1038/s41598-019-38895-y</a>
Alternative languages
Result language
angličtina
Original language name
Photopic light-mediated down-regulation of local α1A-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
Original language 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 α1A-adrenoceptor (α1AAR) 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 α1AAR 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.
Czech name
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Czech description
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Classification
Type
J<sub>imp</sub> - Article in a specialist periodical, which is included in the Web of Science database
CEP classification
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OECD FORD branch
30103 - Neurosciences (including psychophysiology)
Result continuities
Project
<a href="/en/project/GJ18-11795Y" target="_blank" >GJ18-11795Y: Role of retinal neural activity in pathogenesis of autoimmune uveitis</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2019
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Scientific Reports
ISSN
2045-2322
e-ISSN
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Volume of the periodical
9
Issue of the periodical within the volume
February
Country of publishing house
GB - UNITED KINGDOM
Number of pages
15
Pages from-to
"Article 2353"
UT code for WoS article
000459094800034
EID of the result in the Scopus database
2-s2.0-85061787054