Glucocorticoid eye drops are one of the most widely used medications in ophthalmology. However, little is known about the effects of glucocorticoids on corneal epithelial cells that are directly exposed to topically-administered glucocorticoids. Here we investigated the effects of prednisolone, a synthetic glucocorticoid analogue frequently used in the clinic, on corneal epithelial cells. Results showed that prednisolone decreased survival of corneal epithelial cells by inhibiting proliferation and inducing apoptosis in a dose-dependent manner. The levels of mitochondrial reactive oxygen species (mtROS), cleaved caspase-3, and -9 were increased by prednisolone. The effects of prednisolone on apoptosis and mtROS were blocked 1) by the glucocorticoid receptor (GR) antagonist RU-38486, 2) in cells with GR siRNA knockdown, and 3) by treatment with N-acetylcysteine. Transcript levels of pro-inflammatory cytokines were increased in corneal epithelial cells upon hyperosmolar stress, but repressed by prednisolone. In NOD.B10.H2b mice, topical administration of 1% prednisolone increased apoptotic cells in the corneal epithelium. Together, data indicate that prednisolone induces apoptosis in corneal epithelial cells through GR and the intrinsic pathway involving mtROS, caspase-9, and -3. The pro-apoptotic effects of glucocorticoids along with their anti-inflammatory effects should be considered when glucocorticoid eye drops are used in patients with ocular surface disease.

译文

糖皮质激素滴眼液是眼科使用最广泛的药物之一。然而,关于糖皮质激素对直接暴露于局部施用糖皮质激素的角膜上皮细胞的影响知之甚少。在这里,我们研究了泼尼松龙 (一种临床上经常使用的合成糖皮质激素类似物) 对角膜上皮细胞的影响。结果表明,泼尼松龙通过抑制增殖和诱导凋亡以剂量依赖性方式降低了角膜上皮细胞的存活率。泼尼松龙增加了线粒体活性氧 (mtROS),裂解caspase-3和-9的水平。泼尼松龙对细胞凋亡和mtROS的影响被1) 糖皮质激素受体 (GR) 拮抗剂RU-38486阻断,2) 用GR siRNA敲低的细胞中,以及3) 用N-乙酰半胱氨酸处理。高渗应激时,角膜上皮细胞中促炎细胞因子的转录水平增加,但被泼尼松龙抑制。在NOD.B10.H2b小鼠中,局部施用1% 泼尼松龙增加了角膜上皮中的凋亡细胞。总之,数据表明泼尼松龙通过GR和涉及mtROS,caspase-9和-3的内在途径诱导角膜上皮细胞凋亡。当糖皮质激素滴眼液用于眼表疾病患者时,应考虑糖皮质激素的促凋亡作用及其抗炎作用。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录