Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice.
Chronic cigarette smoke causes oxidative damage and apoptosis to retinal pigmented epithelial cells in mice.
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DOI：
10.1371/journal.pone.0003119
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发表时间：
2008-09-01
期刊：
影响因子：
3.7
通讯作者：
Handa, James T.
中科院分区：
文献类型：
--
作者：
Fujihara, Masashi;Nagai, Norihiro;Sussan, Thomas E.;Biswal, Shyam;Handa, James T.
本研究的目的是确定暴露于慢性香烟烟雾的小鼠是否会出现早期年龄相关性黄斑变性（AMD）的特征。将两个月大的C57 B16小鼠暴露于吸烟室中的过滤空气或香烟烟雾中，每天5小时，每周5天，持续6个月。将眼睛固定在2.5%戊二醛/2%多聚甲醛中，并通过透射电子显微镜检查超微结构变化。对侧眼用2%多聚甲醛固定，用8-OHdG免疫标记法检测视网膜色素上皮（RPE）的氧化损伤，TUNEL法检测细胞凋亡。暴露于香烟烟雾的小鼠在计数的85±3.7%的RPE细胞中具有8-OHdG的免疫标记，而对照组为9.5±3.9%（p<0.00001）。暴露于烟雾中的小鼠Bruch膜（1086±332 nm）比暴露于空气中的小鼠Bruch膜（543±132 nm; p = 0.0069）厚。 观察到的两种最明显的超微结构变化（严重程度分级量表为0-3）是基底内折叠的丢失（平均等级差异= 1.98; p<0.0001）和细胞内空泡的增加（平均等级差异= 1.7; p<0.0001）。 暴露于香烟烟雾的小鼠中Bruch膜的超微结构变化幅度较小，但始终表明暴露于香烟烟雾的小鼠中损伤级别显著更高，包括基底层沉积物（平均级别差异= 0.54; p<0.0001）、外胶原层沉积物增加（平均级别差异= 0.59; p = 0.002）和基底层存款连续性增加（平均级别差异= 0.4; p<0.0001）。 TUNEL分析显示，暴露于香烟烟雾的小鼠的凋亡RPE百分比（平均8.0±1.1%）高于室内空气（平均0±0%; p = 0.043）。 暴露于慢性香烟烟雾的小鼠产生氧化损伤的证据，伴随RPE和Bruch膜的超微结构变性以及RPE细胞凋亡。该模型可用于研究烟雾引起的早期AMD变化的机制。
The purpose of this study was to determine whether mice exposed to chronic cigarette smoke develop features of early age-related macular degeneration (AMD). Two month old C57Bl6 mice were exposed to either filtered air or cigarette smoke in a smoking chamber for 5 h/day, 5 days/week for 6 months. Eyes were fixed in 2.5% glutaraldehyde/2% paraformaldehyde and examined for ultrastructural changes by transmission electron microscopy. The contralateral eye was fixed in 2% paraformaldehyde and examined for oxidative injury to the retinal pigmented epithelium (RPE) by 8-oxo-7,8-dihydro-2′-deoxyguanosine (8-OHdG) immunolabeling and apoptosis by TUNEL labeling. Mice exposed to cigarette smoke had immunolabeling for 8-OHdG in 85±3.7% of RPE cells counted compared to 9.5±3.9% in controls (p<0.00001). Bruch membrane was thicker in mice exposed to smoke (1086±332 nm) than those raised in air (543±132 nm; p = 0.0069). The two most pronounced ultrastructural changes (severity grading scale from 0–3) seen were a loss of basal infoldings (mean difference in grade = 1.98; p<0.0001), and an increase in intracellular vacuoles (mean difference in grade = 1.7; p<0.0001). Ultrastructural changes to Bruch membrane in cigarette-smoke exposed mice were smaller in magnitude but consistently demonstrated significantly higher grade injury in cigarette-exposed mice, including basal laminar deposits (mean difference in grade = 0.54; p<0.0001), increased outer collagenous layer deposits (mean difference in grade = 0.59; p = 0.002), and increased basal laminar deposit continuity (mean difference in grade = 0.4; p<0.0001). TUNEL assay showed a higher percentage of apoptotic RPE from mice exposed to cigarette smoke (average 8.0±1.1%) than room air (average 0±0%; p = 0.043). Mice exposed to chronic cigarette smoke develop evidence of oxidative damage with ultrastructural degeneration to the RPE and Bruch membrane, and RPE cell apoptosis. This model could be useful for studying the mechanism of smoke induced changes during early AMD.
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影响因子：
4.4
作者：
Espinosa-Heidmann, DG;Suner, IJ;Cousins, SW
通讯作者：
Cousins, SW
影响因子：
--
作者：
GOTTSCH, JD;BYNOE, LA;GREEN, WR
通讯作者：
GREEN, WR
DOI：
10.1007/bf02154735
发表时间：
1986-01-01
影响因子：
2.7
作者：
LOFFLER, KU;LEE, WR
通讯作者：
LEE, WR
影响因子：
4.2
作者：
FEENEYBURNS, L;BURNS, RP;GAO, CL
通讯作者：
GAO, CL
影响因子：
--
作者：
Klein, Ronald;Knudtson, Michael D.;Klein, Barbara E. K.
通讯作者：
Klein, Barbara E. K.