Photopic light-mediated down-regulation of local α1A -adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis

Scientific Reports
Andrea StofkovaMasaaki Murakami

Abstract

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. T...Continue Reading

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Citations

Apr 8, 2019·Journal of Internal Medicine·D Kamimura, M Murakami
Jan 14, 2020·International Immunology·Haruka HiguchiMasaaki Murakami
Apr 2, 2020·Bioelectronic Medicine·Andrea Stofkova, Masaaki Murakami
Dec 26, 2019·International Immunology·Daisuke KamimuraMasaaki Murakami
Jan 5, 2021·The Journal of Clinical Investigation·Ruijuan GaoErica L Herzog
Aug 28, 2020·Reviews in the Neurosciences·Dorothea DereEkrem Dere
Mar 23, 2021·International Immunology·Akiko NakaiKazuhiro Suzuki
Sep 11, 2021·International Immunology·Kaoru MurakamiMasaaki Murakami

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Methods Mentioned

BETA
flow cytometry
Fluorescence microscopy
FCS
FACS
enzyme-linked immunosorbent assay
protein assay
dissection

Software Mentioned

Preview
ImageJ
BZ II Analyzer
Laser Image Analyzer
GraphPad
FlowJo
Statistica

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