Who let the dogs out?: detrimental role of Galectin-3 in hypoperfusion-induced retinal degeneration.
Who let the dogs out?: detrimental role of Galectin-3 in hypoperfusion-induced retinal degeneration.
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DOI：
10.1186/s12974-015-0312-x
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发表时间：
2015-05-14
影响因子：
9.3
通讯作者：
Taylor L
中科院分区：
文献类型：
--
作者：
Manouchehrian O;Arnér K;Deierborg T;Taylor L
视网膜缺血导致神经元的进行性变性和神经胶质细胞的病理性激活，从而导致视力丧失。在脑中，缺血性损伤后的进行性损伤与涉及小胶质细胞的神经炎症过程相关。半乳糖凝集素-3已被证明介导小胶质细胞对脑中缺血性损伤的反应。因此，我们想要探索半乳糖凝集素-3（Gal-3）对低灌注诱导的小鼠视网膜变性的贡献。Gal-3敲除（Gal-3 KO）和野生型（WT）C57 BL/6小鼠通过使用金属线圈使颈总动脉双侧变窄而经历慢性脑灌注不足，导致血流减少30%。假手术小鼠作为对照。17周后，处死小鼠，并使用形态学染色和免疫组织化学分析眼睛的视网膜结构、神经元细胞存活和神经胶质反应性。低灌注导致WT小鼠中Gal-3表达和小胶质细胞活化的强烈增加，伴随所有视网膜神经元亚型的严重退行性损伤、视网膜层重塑和Müller细胞胶质增生。相比之下，低灌注Gal-3 KO小鼠表现出保留的层状结构，光感受器和神经节细胞神经元的显著保留，以及小胶质细胞和Müller细胞活化的衰减。小鼠中的中度脑血流量减少导致严重的视网膜变性损伤。在缺乏Gal-3表达的小鼠中，病理变化显著减弱。因此，Gal-3是治疗和预防低灌注诱导的视网膜变性的潜在靶标，并且是作为视网膜变性疾病背后的因素进行进一步研究的强有力候选者。本文的在线版本（doi：10.1186/s12974-015-0312-x）包含补充材料，可供授权用户使用。
Retinal ischemia results in a progressive degeneration of neurons and a pathological activation of glial cells, resulting in vision loss. In the brain, progressive damage after ischemic insult has been correlated to neuroinflammatory processes involving microglia. Galectin-3 has been shown to mediate microglial responses to ischemic injury in the brain. Therefore, we wanted to explore the contribution of Galectin-3 (Gal-3) to hypoperfusion-induced retinal degeneration in mice. Gal-3 knockout (Gal-3 KO) and wildtype (WT) C57BL/6 mice were subjected to chronic cerebral hypoperfusion by bilateral narrowing of the common carotid arteries using metal coils resulting in a 30% reduction of blood flow. Sham operated mice served as controls. After 17 weeks, the mice were sacrificed and the eyes were analyzed for retinal architecture, neuronal cell survival, and glial reactivity using morphological staining and immunohistochemistry. Hypoperfusion caused a strong increase in Gal-3 expression and microglial activation in WT mice, coupled with severe degenerative damage to all retinal neuronal subtypes, remodeling of the retinal lamination and Müller cell gliosis. In contrast, hypoperfused Gal-3 KO mice displayed a retained laminar architecture, a significant preservation of photoreceptors and ganglion cell neurons, and an attenuation of microglial and Müller cell activation. Moderate cerebral blood flow reduction in the mouse results in severe retinal degenerative damage. In mice lacking Gal-3 expression, pathological changes are significantly attenuated. Gal-3 is thereby a potential target for treatment and prevention of hypoperfusion-induced retinal degeneration and a strong candidate for further research as a factor behind retinal degenerative disease. The online version of this article (doi:10.1186/s12974-015-0312-x) contains supplementary material, which is available to authorized users.
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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：
4.4
作者：
Jeon, Sae-Bom;Yoon, Hee Jung;Park, Eun Jung
通讯作者：
Park, Eun Jung
影响因子：
3.4
作者：
BARNETT, NL;OSBORNE, NN
通讯作者：
OSBORNE, NN
影响因子：
3.3
作者：
Engelsberg, Karl;Ghosh, Fredrik
通讯作者：
Ghosh, Fredrik
影响因子：
15.1
作者：
Kim BJ;Braun TA;Wordinger RJ;Clark AF
通讯作者：
Clark AF