Inflamed In Vitro Retina: Cytotoxic Neuroinflammation and Galectin-3 Expression.
Inflamed In Vitro Retina: Cytotoxic Neuroinflammation and Galectin-3 Expression.
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体外视网膜发炎：细胞毒性神经炎症和半乳糖素3表达。
DOI：
10.1371/journal.pone.0161723
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发表时间：
2016
期刊：
影响因子：
3.7
通讯作者：
Englund-Johansson U
中科院分区：
文献类型：
--
作者：
Bauer PM;Zalis MC;Abdshill H;Deierborg T;Johansson F;Englund-Johansson U
视网膜神经变性的疾病进展与免疫细胞激活密切相关，免疫细胞激活可能具有神经保护或神经毒性作用。增加对免疫反应和视网膜神经变性的了解可能会导致治疗的候选靶点。因此，我们以异体视网膜为模型，探讨了培养物本身诱导的免疫反应和免疫调节剂Galectin-3(Galectin-3)的表达以及内毒素(LPS)附加免疫刺激后Gal-3的表达及其与视网膜神经毒性的关系。出生后的小鼠视网膜在特定的培养液中培养。一组给予内毒素(100 ng/ml，24 h)刺激。在培养时(0d体外培养)、3d、4d和7d用形态染色、生化和免疫组织化学技术研究视网膜的构筑、细胞凋亡、微胶质细胞和巨胶质细胞的活性。我们的结果表明，大小胶质细胞的持续激活，其特征是没有可检测到的细胞因子释放和Gal-3的有限表达，除了轴突切断诱导的最内核层的凋亡外，并没有进一步诱导细胞凋亡。内毒素刺激后，免疫应答增强，主要表现为免疫介质(IL-2、IL-6、KC/GRO(也称为CLCX1和肿瘤坏死因子-α))的释放、小胶质细胞数量的增加以及Gal-3的表达。伴随而来的是另外两个核层中的细胞凋亡增加，以及对视网膜大体结构的损害。我们证明，免疫反应的特征是持续和增加的细胞因子的释放，伴随着Gal-3表达的增加，伴随着移植视网膜神经毒性的显著增加。利用目前的环境进行进一步的研究可能会加深对视网膜神经退行性变中神经元丢失的机制的理解。
Disease progression in retinal neurodegeneration is strongly correlated to immune cell activation, which may have either a neuroprotective or neurotoxic effect. Increased knowledge about the immune response profile and retinal neurodegeneration may lead to candidate targets for treatments. Therefore, we have used the explanted retina as a model to explore the immune response and expression of the immune modulator galectin-3 (Gal-3), induced by the cultivation per se and after additional immune stimulation with lipopolysaccharide (LPS), and how this correlates with retinal neurotoxicity. Post-natal mouse retinas were cultured in a defined medium. One group was stimulated with LPS (100 ng/ml, 24 h). Retinal architecture, apoptotic cell death, and micro- and macroglial activity were studied at the time of cultivation (0 days in vitro (DIV)) and at 3, 4 and 7 DIV using morphological staining, biochemical- and immunohistochemical techniques. Our results show that sustained activation of macro- and microglia, characterized by no detectable cytokine release and limited expression of Gal-3, is not further inducing apoptosis additional to the axotomy-induced apoptosis in innermost nuclear layer. An elevated immune response was detected after LPS stimulation, as demonstrated primarily by release of immune mediators (i.e. interleukin 2 (IL-2), IL-6, KC/GRO (also known as CLCX1) and tumour necrosis factor-α (TNF-α)), increased numbers of microglia displaying morphologies of late activation stages as well as Gal-3 expression. This was accompanied with increased apoptosis in the two additional nuclear layers, and damage to retinal gross architecture. We demonstrate that an immune response characterized by sustained and increased release of cytokines, along with an increase in Gal-3 expression, is accompanied by significant increased neurotoxicity in the explanted retina. Further investigations using the current setting may lead to increased understanding on the mechanisms involved in neuronal loss in retinal neurodegenerations.
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影响因子：
8.3
作者：
Ito, D;Tanaka, K;Fukuuchi, Y
通讯作者：
Fukuuchi, Y
影响因子：
16.2
作者：
ANKARCRONA, M;DYPBUKT, JM;NICOTERA, P
通讯作者：
NICOTERA, P
影响因子：
3.7
作者：
Ferrer-Martín RM;Martín-Oliva D;Sierra-Martín A;Carrasco MC;Martín-Estebané M;Calvente R;Martín-Guerrero SM;Marín-Teva JL;Navascués J;Cuadros MA
通讯作者：
Cuadros MA
影响因子：
9
作者：
Farinelli P;Perera A;Arango-Gonzalez B;Trifunovic D;Wagner M;Carell T;Biel M;Zrenner E;Michalakis S;Paquet-Durand F;Ekström PA
通讯作者：
Ekström PA
影响因子：
2.5
作者：
Bosco, Alejandra;Steele, Michael R.;Vetter, Monica L.
通讯作者：
Vetter, Monica L.