Photopic light-mediated down-regulation of local α1A-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
Photopic light-mediated down-regulation of local α1A-adrenergic signaling protects blood-retina barrier in experimental autoimmune uveoretinitis
复制标题
明视光介导的局部 α1A 肾上腺素信号传导下调可保护实验性自身免疫性葡萄膜视网膜炎中的血视网膜屏障
DOI：
10.1038/s41598-019-38895-y
复制
发表时间：
2019
影响因子：
4.6
通讯作者：
Murakami Masaaki
中科院分区：
文献类型：
--
作者：
Stofkova Andrea;Kamimura Daisuke;Ohki Takuto;Ota Mitsutoshi;Arima Yasunobu;Murakami Masaaki
我们已经报道了通道反射，它描述了在中枢神经系统（CNS）的特定血管中调节免疫细胞通道的特定神经激活。存在四种类型的通道反射，它们都诱导血脑屏障特定血管内皮细胞的改变，随后在中枢神经系统自身反应性T细胞存在下引起中枢神经系统炎症。在这里，我们报告了一种新的通道反射，通过使用自身反应性T细胞介导的眼部炎症模型来抑制视网膜炎症的发展。暴露于光下可下调肾上腺素受体途径，通过抑制血液视网膜屏障的破坏来减轻眼部炎症。机制分析表明，由于去甲肾上腺素和肾上腺素水平升高，光照射可下调α 1a -肾上腺素受体（α1AAR）的表达，从而抑制炎症反应。手术切除颈上神经节（SCG）并没有否定光的保护作用，这表明受影响的是视网膜去肾上腺素能神经元，而不是SCG的交感神经元。介光下α1AAR信号的阻断再现了光的保护作用。因此，靶向区域肾上腺素能受体信号可能代表一种新的治疗自身免疫性疾病的策略，包括那些影响被屏障隔开的器官（如中枢神经系统和眼睛）的疾病。
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.
登录
查看更多内容
DOI：
10.1002/neu.20200
发表时间：
2006-01-01
期刊：
JOURNAL OF NEUROBIOLOGY
影响因子：
--
作者：
Kraij-Hans, I;Tibber, M;Mobbs, P
通讯作者：
Mobbs, P
影响因子：
15.9
作者：
Usui, Voshihiko;Westenskow, Peter D.;Friedlander, Martin
通讯作者：
Friedlander, Martin
对眼睛的自主控制。
影响因子：
5.8
作者：
McDougal DH;Gamlin PD
通讯作者：
Gamlin PD
影响因子：
4.4
作者：
Peng, Yong;Han, Gencheng;Sun, Deming
通讯作者：
Sun, Deming
大鼠视网膜中存在多巴胺β-羟化酶的生化证据。
影响因子：
2.9
作者：
Park,DH;Joh,TH;Anwar,M;Ruggiero,DA
通讯作者：
Ruggiero,DA