Activation of autophagy induces retinal ganglion cell death in a chronic hypertensive glaucoma model.
Activation of autophagy induces retinal ganglion cell death in a chronic hypertensive glaucoma model.
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DOI：
10.1038/cddis.2012.26
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发表时间：
2012-04-05
影响因子：
9
通讯作者：
中科院分区：
文献类型：
--
作者：
据报道，自噬在调节细胞死亡途径和神经退行性变中具有重要作用。本研究采用慢性高血压性青光眼大鼠模型，探讨自噬通路在慢性高眼压后视网膜神经节细胞（retinal ganglion cells，RGCs）凋亡中的作用。电镜下可见自噬体在视网膜节细胞的树突和胞浆中大量聚集。Western blot分析显示，LC 3-II/LC 3-I和beclin-1在IOP升高后的整个8周期间上调。LC 3免疫染色模式显示视网膜节细胞胞质中的自噬激活增加，并在IOP升高后4周达到峰值。这些LC 3B阳性的RGCs中的大多数通过末端脱氧核苷酸转移酶介导的生物素化UTP缺口末端标记进行凋亡，并且用3-甲基腺嘌呤抑制自噬降低RGC凋亡。激活模式显示，自噬最初在RGC的树突中被激活，但是，此后自噬主要在RGC的细胞质中被激活。这可能表明自噬在神经元的不同隔室中受到不同的调节。本研究表明，自噬在RGCs中被激活，并在慢性IOP升高后的自噬细胞死亡中起作用。
Autophagy is reported to have important roles in relation to regulated cell death pathways and neurodegeneration. This study used chronic hypertensive glaucoma rat model to investigate whether the autophagy pathway has a role in the apoptosis of retinal ganglion cells (RGCs) after chronic intraocular pressure (IOP) elevation. Under electron microscopy, autophagosomes were markedly accumulated in the dendrites and cytoplasm of RGCs after IOP elevation. Western blot analysis showed that LC3-II/LC3-I and beclin-1 were upregulated throughout the 8-weeks period after IOP elevation. The pattern of LC3 immunostaining showed autophagy activation in the cytoplasm of RGCs to increase and peak at 4 weeks after IOP elevation. Most of these LC3B-positive RGCs underwent apoptosis by terminal deoxynucleotidyltransferase-mediated biotinylated UTP nick end labeling, and inhibition of autophagy with 3-methyladenine decreased RGC apoptosis. The activated pattern shows that autophagy is initially activated in the dendrites of the RGCs, but, thereafter autophagy is mainly activated in the cytoplasm of RGCs. This may show that autophagy is differently regulated in different compartments of the neuron. This present study showed that autophgy is activated in RGCs and has a role in autophagic cell death after chronic IOP elevation.
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影响因子：
11.1
作者：
He C;Klionsky DJ
通讯作者：
Klionsky DJ
影响因子：
3.4
作者：
Guo, Ying;Johnson, Elaine;Cepurna, William;Jia, Lijun;Dyck, Jennifer;Morrison, John C.
通讯作者：
Morrison, John C.
影响因子：
3.3
作者：
Mizushima, N;Yamamoto, A;Ohsumi, Y
通讯作者：
Ohsumi, Y
影响因子：
56.9
作者：
RAFF, MC;BARRES, BA;JACOBSON, MD
通讯作者：
JACOBSON, MD
影响因子：
3.7
作者：
Piras A;Gianetto D;Conte D;Bosone A;Vercelli A
通讯作者：
Vercelli A