Kido N, Inatani M, Honjo M, Yoneda S, Hara H, Miyawaki N, Honda Y, Tanihara H
Department of Ophthalmology and Visual Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.
Brain Res. 2001 Aug 10;910(1-2):153-62. doi: 10.1016/s0006-8993(01)02706-8.
In this study we determine if interleukin-1beta (IL-1beta) modulates N-methyl-D-aspartate (NMDA)-induced retinal damage. Sprague-Dawley rats were anesthetized with inhalation of halothane, after which a single injection of 5 microl of IL-1beta (0.1 to 10 ng/eye) (and/or IL-1 receptor antagonist (IL-1ra)) for experimental eyes was administered. Two days later (or simultaneously), NMDA (20 nmol) was injected into the vitreous space. One week later, each eye was enucleated and transverse sections were subjected to morphometric analysis. Enzyme-linked immunosorbent assay (ELISA) was conducted for the determination of IL-1beta levels in retina. Immunohistochemical and immunoblot studies were also performed. In eyes that received an intravitreal injection of IL-1beta (0.1 to 10 ng/eye), significant thinning of the inner plexiform layer (IPL) was observed (P<0.05). Immunohistochemical and ELISA studies demonstrated upregulated expression of IL-1beta in retinas that had undergone NMDA injection. Treatment with 10 ng of IL-1ra induced a protective effect against NMDA-induced retinal damage. Pretreatment with IL-1beta induced a significant protective effect on NMDA-induced retinal damage. Our studies suggest that IL-1beta induces neuronal cell death directly, as shown by the protective effects of IL-1ra, but has a protective effect on NMDA-induced retinal damage indirectly after an incubation time of at least 2 days.
在本研究中，我们确定白细胞介素-1β（IL-1β）是否调节N-甲基-D-天冬氨酸（NMDA）诱导的视网膜损伤。将Sprague-Dawley大鼠用氟烷吸入麻醉，之后向实验眼单次注射5微升IL-1β（0.1至10纳克/眼）（和/或IL-1受体拮抗剂（IL-1ra））。两天后（或同时），将NMDA（20纳摩尔）注入玻璃体腔。一周后，摘除每只眼睛并对横切片进行形态计量分析。进行酶联免疫吸附测定（ELISA）以测定视网膜中的IL-1β水平。还进行了免疫组织化学和免疫印迹研究。在接受玻璃体内注射IL-1β（0.1至10纳克/眼）的眼中，观察到内网状层（IPL）明显变薄（P<0.05）。免疫组织化学和ELISA研究表明，在接受NMDA注射的视网膜中IL-1β表达上调。用10纳克IL-1ra治疗可诱导对NMDA诱导的视网膜损伤的保护作用。用IL-1β预处理可诱导对NMDA诱导的视网膜损伤的显著保护作用。我们的研究表明，如IL-1ra的保护作用所示，IL-1β直接诱导神经元细胞死亡，但在至少2天的孵育时间后，对NMDA诱导的视网膜损伤具有间接保护作用。
