Alteration of retinal intrinsic survival signal and effect of α2-adrenergic receptor agonist in the retina of the chronic ocular hypertension rat
Alteration of retinal intrinsic survival signal and effect of α2-adrenergic receptor agonist in the retina of the chronic ocular hypertension rat
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DOI：
10.1017/s0952523807070150
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发表时间：
2007-03-01
影响因子：
1.9
通讯作者：
Park, Chan Kee
中科院分区：
文献类型：
--
作者：
Kim, Hwa Sun;Chang, Yong Ik;Park, Chan Kee
本研究的目的是检查内在细胞存活分子的视网膜表达，并阐明 α2-肾上腺素受体激动剂在慢性高眼压大鼠模型中的作用。通过巩膜外静脉烧灼在每只大鼠的双眼中诱导慢性高眼压症。将两滴 5 微升选择性 α2-肾上腺素受体激动剂溴莫尼定 0.2%（Alphagan；Allergan Inc.，Irvine，CA，USA）局部给药于一只眼睛，每天两次，持续长达八周。另一只眼接受平衡盐溶液作为对照。在损伤后 1、4 和 8 周评估蛋白质和 mRNA 表达。使用免疫组织化学评估 BDNF、Akt 和 GFAP 的视网膜表达。使用半定量 RT-PCR 测定视网膜 BDNF、bcl-2 和 bcl-xL mRNA 水平。用 4-Di-10-ASP (DiA) 逆行标记后评估视网膜神经节细胞 (RGC) 密度。在高眼压眼中观察到 RGC 密度显着降低。烧灼眼损伤后 1 周起，GFAP 表达增加，bcl-2、bcl-xL 和 BDNF mRNA 表达也增加。用溴莫尼定治疗高眼压眼可减少 RGC 损失、降低 GFAP 免疫反应性水平以及增加 BDNF mRNA 和 p-Akt 表达。溴莫尼定似乎通过涉及 α2-肾上腺素能受体介导的生存信号激活和慢性高眼压大鼠视网膜内源性神经营养因子表达上调的机制来保护 RGC 免受神经变性。
The purpose of this study is to examine the retinal expression of intrinsic cell survival molecules and to elucidate the effect of an alpha 2-adrenergic receptor agonist in the chronic ocular hypertensive rat model. Chronic ocular hypertension was induced in both eyes of each rat by episcleral vein cauterization. Two five-microliter drops of the selective alpha 2-adrenoceptor agonist brimonidine 0.2% (Alphagan; Allergan Inc., Irvine, CA, USA) were topically administered twice daily for up to eight weeks in one eye. The fellow eye received balanced salt solution as a control. Protein and mRNA expression were evaluated at 1, 4, and 8 weeks after injury. Retinal expression of BDNF, Akt, and GFAP was assessed using immunohistochemistry. Retinal levels of mRNA for BDNF, bcl-2, and bcl-xL were determined using semi-quantitative RT-PCR. Retinal ganglion cell (RGC) density was evaluated after retrograde labeling with 4-Di-10-ASP (DiA). A significant decrease in RGC density was observed in ocular hypertensive eyes. Cauterized eyes showed an increase in GFAP expression from one week after injury, and the expression of bcl-2, bcl-xL, and BDNF mRNA was also increased. Treatment of ocular hypertensive eyes with brimonidine resulted in a reduction in RGC loss, a decrease in the level of GFAP immunoreactivity, and an increment in BDNF mRNA and p-Akt expression. Brimonidine appears to protect RGCs from neurodegeneration through mechanisms involving alpha 2-adrenergic receptor mediated survival signal activation and up-regulation of endogenous neurotrophic factor expression in the chronic ocular hypertensive rat retina.