Acriflavine, a HIF-1 inhibitor, preserves vision in an experimental autoimmune encephalomyelitis model of optic neuritis.
Acriflavine, a HIF-1 inhibitor, preserves vision in an experimental autoimmune encephalomyelitis model of optic neuritis.
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HIF-1抑制剂Acriflavine在实验性自身免疫性脑脊髓炎视神经炎模型中保护视力。
DOI：
10.3389/fimmu.2023.1271118
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发表时间：
2023
影响因子：
7.3
通讯作者：
Gramlich, Oliver W.
中科院分区：
文献类型：
--
作者：
Anders, Jeffrey J.;Elwood, Benjamin W.;Kardon, Randy H.;Gramlich, Oliver W.
关键词：
视神经炎（ON）通常是多发性硬化症（MS）的早期体征，最近的研究表明HIF-1通路激活与炎症之间存在联系。本研究旨在确定在实验性自身免疫性脑脊髓炎（EAE）ON模型中，使用HIF-1a拮抗剂acriflavine（ACF）抑制HIF-1通路是否可以减少临床进展并挽救眼部表型。通过用MOG 33 -55免疫60只雌性C57 BL/6 J小鼠诱导EAE相关的ON，并且20只EAE小鼠每天接受5 mg/kg的ACF全身注射。将ACF处理的EAE小鼠的视觉功能和结构的变化与安慰剂注射的EAE小鼠和未处理的对照小鼠的视觉功能和结构的变化进行比较。ACF治疗沿着改善了运动感觉障碍，同时保留了视力和视神经功能。对视网膜神经节细胞复合体的分析也表明，视网膜神经节细胞及其轴突的存活率增加与厚度的保持相关。ACF处理的EAE小鼠的视神经细胞浸润和脱髓鞘程度减少。随后的体外研究显示，改善不仅归因于HIF-1的抑制，而且还归因于先前未被认识到的与未折叠蛋白反应途径中的eIF 2a/ATF 4轴的相互作用。本研究表明，ACF通过其对HIF-1和UPR信号通路的多效性抑制作用对MS动物模型有效，可能是促进MS康复的可行方法。
Optic neuritis (ON) is often an early sign of multiple sclerosis (MS), and recent studies show a link between HIF-1 pathway activation and inflammation. This study aimed to determine if inhibition of the HIF-1 pathway using the HIF-1a antagonist acriflavine (ACF) can reduce clinical progression and rescue the ocular phenotype in an experimental autoimmune encephalomyelitis (EAE) ON model. EAE-related ON was induced in 60 female C57BL/6J mice by immunization with MOG33-55, and 20 EAE mice received daily systemic injections of ACF at 5 mg/kg. Changes in the visual function and structure of ACF-treated EAE mice were compared to those of placebo-injected EAE mice and naïve control mice. ACF treatment improved motor–sensory impairment along with preserving visual acuity and optic nerve function. Analysis of retinal ganglion cell complex alsoshowed preserved thickness correlating with increased survival of retinal ganglion cells and their axons. Optic nerve cell infiltration and magnitude of demyelination were decreased in ACF-treated EAE mice. Subsequent in vitro studies revealed improvements not only attributed to the inhibition of HIF-1 butalso to previously unappreciated interaction with the eIF2a/ATF4 axis in the unfolded protein response pathway. This study suggests that ACF treatment is effective in an animal model of MS via its pleiotropic effects on the inhibition of HIF-1 and UPR signaling, and it may be a viable approach to promote rehabilitation in MS.
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DOI：
10.1093/brain/awu335
发表时间：
2015-01
期刊：
Brain : a journal of neurology
影响因子：
--
作者：
Balcer LJ;Miller DH;Reingold SC;Cohen JA
通讯作者：
Cohen JA
影响因子：
23.9
作者：
Allan KC;Hu LR;Scavuzzo MA;Morton AR;Gevorgyan AS;Cohn EF;Clayton BLL;Bederman IR;Hung S;Bartels CF;Madhavan M;Tesar PJ
通讯作者：
Tesar PJ
影响因子：
15.9
作者：
Kapell, Hannah;Fazio, Luca;Dyckow, Julia;Schwarz, Sophia;Cruz-Herranz, Andres;Mayer, Christina;Campos, Joaquin;D'Este, Elisa;Moebius, Wiebke;Cordano, Christian;Probstel, Anne-Katrin;Gharagozloo, Marjan;Zulji, Amel;Naik, Venu Narayanan;Delank, Anna;Cerina, Manuela;Muentefering, Thomas;Lerma-Martin, Celia;Sonner, Jana K.;Sin, Jung Hyung;Disse, Paul;Rychlik, Nicole;Sabeur, Khalida;Chavali, Manideep;Srivastava, Rajneesh;Heidenreich, Matthias;Fitzgerald, Kathryn C.;Seebohm, Guiscard;Stadelmann, Christine;Hemmer, Bernhard;Platten, Michael;Jentsch, Thomas J.;Engelhardt, Maren;Budde, Thomas;Nave, Klaus-Armin;Calabresi, Peter A.;Friese, Manuel A.;Green, Ari J.;Acuna, Claudio;Rowitch, David H.;Meuth, Seven G.;Schirmer, Lucas
通讯作者：
Schirmer, Lucas
影响因子：
--
作者：
Chari DM
通讯作者：
Chari DM
影响因子：
3.4
作者：
Geeraerts, E.;Dekeyster, E.;Moons, L.
通讯作者：
Moons, L.