Expression of leukemia inhibitory factor in the rat retina following acute ocular hypertension.
Expression of leukemia inhibitory factor in the rat retina following acute ocular hypertension.
复制标题
急性高眼压大鼠视网膜白血病抑制因子的表达。
DOI：
10.3892/mmr.2015.4287
复制
发表时间：
2015-11
影响因子：
3.4
通讯作者：
Wu R
中科院分区：
文献类型：
--
作者：
Hu Q;Huang C;Wang Y;Wu R
本研究旨在探讨急性高眼压大鼠视网膜中白血病抑制因子（LIF）的表达及其下游信号通路。前房灌注生理盐水使大鼠眼压升高至110 mmHg，持续1 h。分别于高眼压终止后12 h、24 h、2 d、3 d、7 d取视网膜组织。苏木精-伊红染色观察视网膜细胞形态学改变，TUNEL法检测视网膜细胞凋亡。使用荧光金逆行（FG）染色进行视网膜神经节细胞（RGC）的定量。免疫印迹法检测急性高眼压后不同时间点眼组织中LIF、LIF受体（LIFR）、信号转导和转录激活因子3（STAT 3）、磷酸化STAT 3（P-STAT 3）、Akt、磷酸化Akt（P-Akt）、细胞外信号调节激酶（ERK）和磷酸化ERK（P-ERK）的表达水平。逆转录-定量聚合酶链反应检测LIF和LIFR mRNA表达水平。结果显示，再灌注后12 h、24 h、2、3、7 d，视网膜内核层和内网状层厚度减少，视网膜节细胞数量减少。急性高眼压后LIF和LIFR的表达水平升高。视网膜再灌注12 h后，P-STAT 3和P-Akt表达明显上调，而P-ERK表达下降。LIF和LIFR表达水平的变化提示LIF可能通过激活Janus激酶/STAT和Akt信号通路在急性高眼压诱导的视网膜缺血后的变性/保护过程中起重要作用。
The aim of the present study was to investigate the expression of leukemia inhibitory factor (LIF) and its downstream signaling pathways in the rat retina following acute ocular hypertension. The intraocular pressure of the rats was elevated to 110 mmHg for 1 h by infusing the anterior chamber with normal saline. The retinal tissues were obtained 12 h, 24 h, and 2, 3 and 7 days after termination of the ocular hypertension. Hematoxylin and eosin and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining were performed to assess the morphological changes and the apoptosis of retinal cells, respectively. Quantification of the retinal ganglion cells (RGCs) was performed using fluorogold retrograde (FG) staining. The expression levels of LIF, LIF receptor (LIFR), signal transducers and activators of transcription 3 (STAT3), phosphorylated STAT3 (P-STAT3), Akt, phosphorylated-Akt (P-Akt), extracellular signal-regulated kinase (ERK) and phosphorylated ERK (P-ERK) were determined at different time-points following acute ocular hypertension using western blot analysis. Reverse transcription-quantitative polymerase chain reaction was performned to detect the mRNA expression levels of LIF and LIFR. The results revealed that 12 h, 24 h, 2, 3 and 7 days after reperfusion, the thickness of the inner nuclear layer and the inner plexiform layer was decreased, with a significant reduction in the number of RGCs, as determined using TUNEL and FG staining. The expression levels of LIF and LIFR were increased following acute ocular hypertension. At 12 h post-retinal reperfusion, the expression levels of P-STAT3 and P-Akt were significantly upregulated, while the expression of P-ERK was decreased. The changes in the expression levels of LIF and LIFR suggested that LIF may be important in the process of degeneration/protection following retinal ischemia induced by acute ocular hypertension, via activation of the Janus kinase/STAT and Akt signaling pathways.