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长期研究中白化大鼠的光诱导视网膜病变。一种免疫组织化学和定量方法。

Light-induced retinopathy in the albino rat in long-term studies. An immunohistochemical and quantitative approach.

作者信息

Pérez J, Perentes E

机构信息

Sandoz Pharma Ltd., Drug Safety Assessment/Toxicology, Basle, Switzerland.

出版信息

Exp Toxicol Pathol. 1994 Aug;46(3):229-35. doi: 10.1016/S0940-2993(11)80088-6.

Abstract

Retinas from male Wistar rats which were housed during a long-term drug safety study at short, medium and long distance from a fluorescent light source were examined. Retinal atrophy was pronounced in the central retina of rats housed closest to the light source, and was characterized by a loss of photoreceptor cells and of S-antigen immunoreactivity in the outer nuclear layer (ONL), absence of synaptophysin immunoreactivity in the outer plexiform layer (OPL), decrease of the number of nuclei in the inner nuclear layer (INL), astrocytic proliferation, and Müller cell activation. The peripheral retina of these rats had a laminated architecture, although the number of photoreceptor cells and nuclei in the INL was reduced. Retinas from rats housed a medium distance from the light source did not have any apparent histological or immunohistochemical changes, except for a lower number of photoreceptor cells and nuclei in the INL. The rats housed a long distance from the light source had the highest number of nuclei in the ONL and INL of the central and peripheral retina, and were used as control group. Our data indicate that retinal atrophy occurs in male Wistar rats maintained under light conditions currently used in long-term toxicity studies, and suggest that photoreceptor cell loss is followed by trans-synaptic anterograde degeneration of neurons in the INL, astrocytic proliferation and Müller cell activation.

摘要

对在长期药物安全性研究期间饲养于距荧光光源短、中、远距离的雄性Wistar大鼠的视网膜进行了检查。饲养在最靠近光源处的大鼠,其视网膜中央萎缩明显,特征为光感受器细胞丢失、外核层(ONL)中S抗原免疫反应性丧失、外丛状层(OPL)中突触素免疫反应性缺失、内核层(INL)细胞核数量减少、星形细胞增殖以及Müller细胞活化。这些大鼠的周边视网膜具有分层结构,尽管INL中的光感受器细胞和细胞核数量减少。饲养在距光源中等距离处的大鼠,除了INL中的光感受器细胞和细胞核数量较少外,没有任何明显的组织学或免疫组织化学变化。饲养在距光源远距离处的大鼠,其中央和周边视网膜的ONL和INL中的细胞核数量最多,用作对照组。我们的数据表明,在长期毒性研究目前使用的光照条件下饲养的雄性Wistar大鼠会发生视网膜萎缩,并表明光感受器细胞丢失后会伴随INL中神经元的跨突触顺行性变性、星形细胞增殖和Müller细胞活化。

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