Department of Ophthalmology and Visual Science, Seoul St. Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea.
Cell Death Dis. 2012 Apr 5;3(4):e290. doi: 10.1038/cddis.2012.26.
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.
自噬被报道在调节细胞死亡途径和神经退行性变方面具有重要作用。本研究使用慢性高血压性青光眼大鼠模型，探讨自噬途径在慢性眼压升高后视网膜神经节细胞 (RGC) 凋亡中的作用。在电子显微镜下，眼压升高后，RGC 的树突和细胞质中明显积累了自噬体。Western blot 分析显示，LC3-II/LC3-I 和 beclin-1 在眼压升高后 8 周内持续上调。LC3 免疫染色的模式显示，自噬在 RGC 的细胞质中被激活并在眼压升高后 4 周达到峰值。大多数这些 LC3B 阳性的 RGC 经历了由末端脱氧核苷酸转移酶介导的生物素化 UTP 缺口末端标记的凋亡，并且自噬的抑制通过 3-甲基腺嘌呤降低了 RGC 凋亡。激活的模式表明，自噬最初在 RGC 的树突中被激活，但此后自噬主要在 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 RGC 中被激活，并在慢性眼压升高后自噬性细胞死亡中起作用。
