The role of apoptosis within the retina of coronavirus-infected mice.
The role of apoptosis within the retina of coronavirus-infected mice.
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发表时间：
2000-09
影响因子：
4.4
通讯作者：
Yun Wang;B. Detrick;Zuxi Yu;Jun Zhang;L. Chesky;J. Hooks
中科院分区：
文献类型：
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作者：
Yun Wang;B. Detrick;Zuxi Yu;Jun Zhang;L. Chesky;J. Hooks
目的探讨细胞凋亡在冠状病毒诱导的小鼠视网膜病变中的可能作用。方法小鼠玻璃体内接种病毒。用苏木精-伊红染色、免疫组织化学染色、原位末端脱氧核糖核酸转移酶dUTP缺口末端标记(TUNEL)和电子显微镜等方法对接种后不同时间的小鼠眼进行细胞凋亡和免疫学检测。对分离的视网膜进行感染性病毒和凋亡相关基因的表达分析。结果BALB/c和CD-1小鼠感染眼细胞凋亡数明显增加，第6~10天达高峰，第20天恢复正常。相比之下，在正常或模拟注射的小鼠眼睛中观察到很少的凋亡细胞。视网膜内的细胞凋亡事件与病毒抗原的存在、CD8(+)T细胞的渗透和感染性病毒的清除有关。逆转录-聚合酶链式反应(RT-PCR)检测到感染视网膜中Fas配体(FasL)和颗粒酶B的mRNAs表达上调。视网膜变性易感(BALB/c)和耐药(CD-1)小鼠在细胞凋亡、调控基因表达和病毒清除方面的发展相似。结论视网膜细胞凋亡与视网膜炎症、感染性病毒的减少和CTL杀伤相关基因的上调有关。这些研究表明，视网膜细胞凋亡可能是限制这种视网膜感染的宿主机制之一。
PURPOSE To evaluate the possible roles of apoptosis in the murine retinopathy induced by coronavirus. METHODS Mice were inoculated with virus intravitreally. Mouse eyes harvested at varying times after inoculation were evaluated for apoptotic and immunologic events by hematoxylin and eosin staining, immunohistochemical staining, in situ terminal deoxynucleotidyltransferase dUTP nick-end labeling (TUNEL) assay, and electron microscopy. Isolated retinas were analyzed for infectious virus and for expression of apoptosis-associated genes. RESULTS The number of apoptotic events was significantly elevated in infected eyes from BALB/c and CD-1 mouse strains, reaching a maximum at days 6 through 10, and returning to normal levels at day 20. The majority of apoptotic cells were observed in the outer nuclear layer of the infected retina. In contrast, few apoptotic cells were observed in normal or mock-injected mouse eyes. Apoptotic events within the retina were associated with the presence of viral antigen, infiltration of CD8(+) T cells, and clearance of infectious virus. Reverse transcription-polymerase chain reaction (RT-PCR) analysis identified the upregulation of Fas ligand (FasL) and granzyme B mRNAs within the infected retinas. The development of apoptosis, regulative gene expression, and viral clearance were similar in both retinal degeneration-susceptible (BALB/c) and -resistant (CD-1) mice. CONCLUSIONS Retinal apoptosis was associated with retinal inflammation, a decrease in infectious virus, and upregulation of genes associated with CTL killing. These studies indicate that retinal apoptosis may be one of the host mechanisms that contribute to limiting this retinal infection.