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用猴水痘病毒对猴子进行眼内接种:临床和组织病理学观察。

Ocular inoculation of monkeys with simian varicella virus: clinical and histopathologic observations.

作者信息

Metcalf J F, Christianson M D, Brady A G

机构信息

Department of Ophthalmology, College of Medicine, University of South Alabama, Mobile 36688.

出版信息

Invest Ophthalmol Vis Sci. 1995 Jan;36(1):41-51.

PMID:7822158
Abstract

PURPOSE

To explore the possibility that inoculation of the eyes of African green monkeys with simian varicella virus (SVV) induces the symptoms of herpes zoster ophthalmicus (HZO), as seen in humans, and to develop a realistic and reproducible animal model of herpes zoster ophthalmicus for experimental studies.

METHODS

In the first experiment, the right eyes of three African green monkeys were inoculated by intrastromal and subconjunctival injections with a suspension of SVV-infected Vero cells. In the second experiment, three additional monkeys were pretreated with intramuscular injections of methylprednisolone (41 mg/kg) for 7 days before ocular inoculation with SVV and for 3 weeks at 14 mg/kg after virus inoculation. The eyes were examined by slit-lamp biomicroscopy. Histologic, immunohistochemical, and electron microscopic studies were performed.

RESULTS

In the first experiment, all three animals developed high titers of anti-SVV antibodies (IgG). Diffuse stromal opacity, with keratitic precipitates, stromal edema, and mild vascularization of the cornea, appeared 12 to 14 days after inoculation. The onset of ocular disease was correlated with the rise in serum antibody levels. There was no clinical evidence of a systemic viral infection resulting from the corneal inoculations in these monkeys. In the second experiment, all three animals treated with methylprednisolone developed severe ocular pathology within 1 week of inoculation. The clinical appearance of the diseased eyes strongly indicated that local viral infection had occurred. Dendritiform keratitis, corneal erosion, and stromal necrosis with vascularization of the cornea was seen in all the eyes. The disease resolved within 4 to 5 weeks of inoculation, leaving opaque, vascularized corneas. Histologic studies showed that inflammatory cells and viral antigens were widespread throughout the diseased corneas. A high titer of anti-SVV antibody (IgG) was detected in the immunosuppressed monkeys, but no evidence of systemic viral infection was observed.

CONCLUSIONS

The authors propose that inoculation of the eyes of methylprednisolone-treated African green monkeys with simian varicella virus provides an appropriate animal model for studies of the virology and immunopathology of ocular varicella virus infection.

摘要

目的

探讨用猴水痘病毒(SVV)接种非洲绿猴眼睛是否会诱发人类所见的眼部带状疱疹(HZO)症状,并建立一种用于实验研究的真实且可重复的眼部带状疱疹动物模型。

方法

在第一个实验中,通过基质内和结膜下注射将感染SVV的Vero细胞悬液接种到三只非洲绿猴的右眼。在第二个实验中,另外三只猴子在眼部接种SVV前7天接受肌肉注射甲泼尼龙(41mg/kg)预处理,并在病毒接种后以14mg/kg的剂量持续3周。通过裂隙灯生物显微镜检查眼睛。进行了组织学、免疫组织化学和电子显微镜研究。

结果

在第一个实验中,所有三只动物都产生了高滴度的抗SVV抗体(IgG)。接种后12至14天出现弥漫性基质混浊,伴有角膜后沉着物、基质水肿和角膜轻度血管化。眼部疾病的发作与血清抗体水平的升高相关。这些猴子角膜接种后没有全身性病毒感染的临床证据。在第二个实验中,所有三只接受甲泼尼龙治疗的动物在接种后1周内出现严重的眼部病变。患病眼睛的临床表现强烈表明发生了局部病毒感染。所有眼睛均出现树枝状角膜炎、角膜糜烂和伴有角膜血管化的基质坏死。疾病在接种后4至5周内消退,留下不透明、血管化的角膜。组织学研究表明,炎性细胞和病毒抗原广泛分布于患病角膜。在免疫抑制的猴子中检测到高滴度的抗SVV抗体(IgG),但未观察到全身性病毒感染的证据。

结论

作者提出,用猴水痘病毒接种经甲泼尼龙治疗的非洲绿猴眼睛,为眼部水痘病毒感染的病毒学和免疫病理学研究提供了一种合适的动物模型。

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Invest Ophthalmol Vis Sci. 1995 Jan;36(1):41-51.
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