Activation of autophagy in a rat model of retinal ischemia following high intraocular pressure.
Activation of autophagy in a rat model of retinal ischemia following high intraocular pressure.
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DOI：
10.1371/journal.pone.0022514
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发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Vercelli A
中科院分区：
文献类型：
--
作者：
Piras A;Gianetto D;Conte D;Bosone A;Vercelli A
急性原发性开角型青光眼是一种以眼压升高为特征的视神经病变，可引起视网膜缺血和神经元死亡。大鼠缺血/再灌注后24小时，辣根过氧化物酶（HRP）或荧光葡聚糖对神经节细胞层（GCL）神经元的内吞作用增强。我们利用酸性磷酸酶（AP）组织化学和免疫荧光对LC3和LAMP1研究了缺血/再灌注后gcl神经元自噬的激活。视网膜I/R导致ap阳性颗粒和lamp1阳性囊泡在损伤后12和24小时出现，24小时LC3标记，并诱导视网膜神经元一致死亡。48 h时，视网膜自噬标志物呈阴性。此外，Western Blot分析显示损伤后LC3水平升高：LC3- ii共轭异构体的增加提示自噬活性。3-甲基腺苷对自噬的抑制部分阻止了神经元的死亡，并在损伤后24小时降低了凋亡标志物。I/R后，大鼠GCL神经元数量显著减少（I/R为12.21±1.13，对照组为19.23±1.12个细胞/500µm）；3-甲基腺嘌呤（17.08±1.42个细胞/500µm）有效抑制自噬体的成熟，部分阻止了这种下降。治疗还可以阻止I/R引起的胶质原纤维酸蛋白免疫反应性的增加。因此，靶向自噬可能是一种治疗青光眼和视网膜缺血的新方法。
Acute primary open angle glaucoma is an optic neuropathy characterized by the elevation of intraocular pressure, which causes retinal ischemia and neuronal death. Rat ischemia/reperfusion enhances endocytosis of both horseradish peroxidase (HRP) or fluorescent dextran into ganglion cell layer (GCL) neurons 24 h after the insult. We investigated the activation of autophagy in GCL-neurons following ischemia/reperfusion, using acid phosphatase (AP) histochemistry and immunofluorescence against LC3 and LAMP1. Retinal I/R lead to the appearance of AP-positive granules and LAMP1-positive vesicles 12 and 24 h after the insult, and LC3 labelling at 24 h, and induced a consistent retinal neuron death. At 48 h the retina was negative for autophagic markers. In addition, Western Blot analysis revealed an increase of LC3 levels after damage: the increase in the conjugated, LC3-II isoform is suggestive of autophagic activity. Inhibition of autophagy by 3-methyladenine partially prevented death of neurons and reduces apoptotic markers, 24 h post-lesion. The number of neurons in the GCL decreased significantly following I/R (I/R 12.21±1.13 vs controls 19.23±1.12 cells/500 µm); this decrease was partially prevented by 3-methyladenine (17.08±1.42 cells/500 µm), which potently inhibits maturation of autophagosomes. Treatment also prevented the increase in glial fibrillary acid protein immunoreactivity elicited by I/R. Therefore, targeting autophagy could represent a novel and promising treatment for glaucoma and retinal ischemia.
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影响因子：
2.5
作者：
CLARKE, PGH
通讯作者：
CLARKE, PGH
影响因子：
4.7
作者：
García-Sevilla, JA;Ferrer-Alcón, M;Maldonado, R
通讯作者：
Maldonado, R
影响因子：
--
作者：
ABERCROMBIE, M
通讯作者：
ABERCROMBIE, M
影响因子：
1.7
作者：
Arnold, A C
通讯作者：
Arnold, A C
影响因子：
6.1
作者：
Carloni, Silvia;Buonocore, Giuseppe;Balduini, Walter
通讯作者：
Balduini, Walter