Different contributions of autophagy to retinal ganglion cell death in the diabetic and glaucomatous retinas.
Different contributions of autophagy to retinal ganglion cell death in the diabetic and glaucomatous retinas.
复制标题
自噬对糖尿病和青光眼视网膜中视网膜神经节细胞死亡的不同贡献。
DOI：
10.1038/s41598-018-30165-7
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发表时间：
2018-09-06
影响因子：
4.6
通讯作者：
Park CK
中科院分区：
文献类型：
--
作者：
Park HL;Kim JH;Park CK
糖尿病和青光眼是选择性视网膜神经节细胞（RGC）死亡的两大原因。为了确定自噬与RGC死亡之间的关系，我们比较了糖尿病视网膜和青光眼视网膜的自噬及其相关分子通路，并研究了它们对RGC存活的影响。对微管相关蛋白轻链3 (LC3)-II和beclin-1进行生化分析。为了确定自噬诱导的途径，我们还探索了腺苷单磷酸活化蛋白激酶（AMPK）和雷帕霉素（mTOR）的机制靶点。青光眼诱导后4周和8周Beclin-1和LC3B-II / LC3B-I比值显著升高；然而，糖尿病视网膜只有轻微的增加。在糖尿病视网膜中，AMPK磷酸化明显上调，mTOR磷酸化明显下调。3-甲基腺嘌呤（3-MA）抑制自噬后，糖尿病视网膜RGCs的凋亡明显增加。然而，3-MA抑制自噬可减少青光眼视网膜RGCs的凋亡。因此，我们的研究结果表明，自噬对RGC死亡的调节是不同的，所涉及的途径取决于触发损伤。
Diabetes mellitus and glaucoma are the two major causes of selective retinal ganglion cell (RGC) death. To determine the relationship between autophagy and RGC death, we compared autophagy and the related molecular pathways in diabetic and glaucomatous retinas and examined their effect on RGC survival. Biochemical analysis of microtubule-associated protein light chain 3 (LC3)-II and beclin-1 were observed. To determine the pathways involved in autophagy induction, adenosine monophosphate-activated protein kinase (AMPK) and the mechanistic target of rapamycin (mTOR) were also explored. Beclin-1 and the LC3B-II to LC3B-I ratio significantly elevated at 4 and 8 weeks after glaucoma induction; however, only a slight increase was apparent in the diabetic retina. Significant upregulation of phosphorylated AMPK and downregulation of phosphorylated mTOR was evident in the diabetic retina. After autophagy was inhibited with 3-methyladenine (3-MA), apoptosis of RGCs was significantly increased in the diabetic retinas. However, 3-MA inhibition of autophagy decreased the apoptosis of RGCs in glaucomatous retinas. Therefore, our results suggest that RGC death is differentially regulated by autophagy and that the pathways involved differ depending on the triggering injury.
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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：
4
作者：
Ng, Dorothy S. K.;Chiang, Peggy P. C.;Ikram, Mohammad K.
通讯作者：
Ikram, Mohammad K.
影响因子：
9
作者：
通讯作者：
--
自噬在眼部健康中的不断演变的功能：一把双刃剑。
影响因子：
9.2
作者：
Chai P;Ni H;Zhang H;Fan X
通讯作者：
Fan X
影响因子：
3.7
作者：
Piras A;Gianetto D;Conte D;Bosone A;Vercelli A
通讯作者：
Vercelli A